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Volume 17
Issue 5
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Viruses, Volume 17, Issue 5 (May 2025) – 149 articles

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18 pages, 842 KiB  
Review
Recombinant Sendai Virus Vectors as Novel Vaccine Candidates Against Animal Viruses
by Álex Gómez and Ramsés Reina
Viruses 2025, 17(5), 737; https://doi.org/10.3390/v17050737 - 21 May 2025
Abstract
Vaccination plays a pivotal role in the control and prevention of animal infectious diseases. However, no efficient and safe universal vaccines are currently registered for major pathogens such as influenza A virus, foot-and-mouth disease virus (FMDV), simian immunodeficiency virus (SIV), and small ruminant [...] Read more.
Vaccination plays a pivotal role in the control and prevention of animal infectious diseases. However, no efficient and safe universal vaccines are currently registered for major pathogens such as influenza A virus, foot-and-mouth disease virus (FMDV), simian immunodeficiency virus (SIV), and small ruminant lentiviruses (SRLV). Here, we review the development of Sendai virus (SeV) vectors as a promising vaccine platform for animal diseases. Recombinant SeV vectors (rSeVv) possess several key features that make them highly suitable for developing vaccination strategies: (1) SeV has exclusively cytoplasmic replication cycle, therefore incapable of transforming host cells by integrating into the cellular genome, (2) rSeVv can accommodate large foreign gene/s inserts (~5 kb) with strong but adjustable transgene expression, (3) can be propagated to high titers in both embryonated chicken eggs and mammalian cell lines, (4) exhibits potent infectivity across a broad range of mammalian cells from different animals species, (5) undergo transient replication in the upper and lower respiratory tracts of non-natural hosts, (6) has not been associated with disease in pigs, non-humans primates, and small ruminants, ensuring a favorable safety profile, and (7) induce a robust innate and cellular immune responses. Preclinical and clinical studies using rSeVv-based vaccines against influenza A virus, FMDV, SIV, and SRLV have yielded promising results. Therefore, this review highlights the potential of rSeVv-based vaccine platforms as a valuable strategy for combating animal viruses. Full article
(This article belongs to the Special Issue Advances in Endemic and Emerging Viral Diseases in Livestock)
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20 pages, 2135 KiB  
Article
Epidemiological and Molecular Surveillance of Aichi Virus A at Different Stages of Sewage Treatment: A One-Year Study in the Southeast of Brazil
by Mariah C. A. do Nascimento, Camila R. Rosa, Meriane Demoliner, Dayla B. Geraldini, Guilherme R. F. Campos, Daniela M. Quevedo, Rafael N. Miceli, Fernando R. Spilki, João Pessoa Araújo, Jr., Marilia F. Calmon and Paula Rahal
Viruses 2025, 17(5), 736; https://doi.org/10.3390/v17050736 - 21 May 2025
Abstract
Enteric viruses, such as the Aichi virus (AiV), pose a potential health risk due to their high excretion rates through fecal elimination, limited removal during treatment processes, and prolonged survival, highlighting the need to assess the potential for exposure and disease transmission through [...] Read more.
Enteric viruses, such as the Aichi virus (AiV), pose a potential health risk due to their high excretion rates through fecal elimination, limited removal during treatment processes, and prolonged survival, highlighting the need to assess the potential for exposure and disease transmission through sanitation systems. This study investigated the prevalence of AiV at three key stages of sewage treatment in the city of São José do Rio Preto, São Paulo state, Brazil, as well as its viral concentrations, infectious potential, and molecular characterization. The data were also analyzed for potential correlations with reported diarrheal disease cases in the city and the physicochemical properties of sewage. The methodology employed included Nested PCR, qPCR, Sanger Sequencing, and phylogenetic analysis, as well as infectivity testing in cell cultures. The prevalence of AiV throughout the year in raw sewage samples was 90.4%, 78.8% in post-anaerobic biological treatment, and 71.1% in post-chemical treatment, totaling 125 positive samples out of 156, being characterized as AiV genotype A. The virus also demonstrated persistence and infectious potential at all three stages analyzed. The AiV-A mean concentration ranged from 2.05 log10 to 4.64 GC/mL, 2.31 to 4.72 log10 GC/mL, and 2.13 to 2.85 log10 GC/mL for the same treatment stages, respectively. A significant difference (p ≤ 0.05) suggests higher viral concentrations in summer at the three sewage process points analyzed, while lower viral concentrations were observed in post-chemical treatment samples (p ≤ 0.01). Additionally, no statistically significant relationship was observed between the virus occurrence in samples and cases of acute diarrheal diseases in the city. In conclusion, this study highlights that much remains to be understood about AiV while providing valuable insights into the relationship between AiV, environmental factors, and public health. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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20 pages, 1384 KiB  
Review
The Function of TRIM25 in Antiviral Defense and Viral Immune Evasion
by Qianxun Liu, Shantong Peng, Jiani Wei and Zhenzhen Xie
Viruses 2025, 17(5), 735; https://doi.org/10.3390/v17050735 - 20 May 2025
Abstract
Tripartite motif (TRIM) 25 is a member of the TRIM E3 ubiquitin ligase family, which plays multiple roles in anti-tumor and antiviral defenses through various pathways. Its RBCC and SPRY/PRY domains work cooperatively for its oligomerization and subsequent activation of ligase activity. TRIM25 [...] Read more.
Tripartite motif (TRIM) 25 is a member of the TRIM E3 ubiquitin ligase family, which plays multiple roles in anti-tumor and antiviral defenses through various pathways. Its RBCC and SPRY/PRY domains work cooperatively for its oligomerization and subsequent activation of ligase activity. TRIM25 expression is regulated by several proteins and RNAs, and it functionally participates in the post-transcriptional and translational modification of antiviral regulators, such as RIG-I, ZAP, and avSGs. Conversely, the antiviral functions of TRIM25 are inhibited by viral proteins and RNAs through their interactions, as well as by the viral infection-mediated upregulation of certain miRNAs. Here, we review the antiviral functions of TRIM25 and highlight its significance regarding innate immunity, particularly in antiviral defense and viral immune evasion. Full article
(This article belongs to the Section Animal Viruses)
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23 pages, 1939 KiB  
Article
Phylogenetic Analysis and Spread of HPAI H5N1 in Middle Eastern Countries Based on Hemagglutinin and Neuraminidase Gene Sequences
by Laith N. AL-Eitan, Diana L. Almahdawi and Iliya Y. Khair
Viruses 2025, 17(5), 734; https://doi.org/10.3390/v17050734 - 20 May 2025
Abstract
Highly pathogenic avian influenza (HPAI) A/H5N1 viruses threaten animal and human health worldwide. The first documented cases in the Middle East were reported in 2005; however, despite extensive phylogenetic studies, there is limited information on the transmission dynamics of the virus within this [...] Read more.
Highly pathogenic avian influenza (HPAI) A/H5N1 viruses threaten animal and human health worldwide. The first documented cases in the Middle East were reported in 2005; however, despite extensive phylogenetic studies, there is limited information on the transmission dynamics of the virus within this region. We analyzed HA and NA gene sequences from various hosts to address this gap and to understand the virus’s spread and evolution in the Middle East. We hypothesized that H5N1 transmission exhibits host-specific or geographically influenced clade structures in this region. This study traced transmission pathways of HPAI A/H5N1 through a phylogenetic and amino acid sequence analysis of HA and NA gene segments from isolates across different hosts in Middle Eastern countries, using the MUSCLE algorithm for alignments and MEGA11 software for phylogenetic analysis. Sequences were selected from NCBI’s virus database based on geographic and host diversity, including those from birds, humans, and other mammals, and were collected at different time points, predominantly after the early 2000s. An amino acid phylogenetic tree was also constructed to examine the conservation of key HA and NA protein residues, identifying distinct clades linked to specific countries and host species, suggesting a possible interspecies transmission and cross-border spread distinct between Egypt and neighboring countries. These findings underscore the role of migratory birds in regional transmission and point to the need for more targeted surveillance and biosecurity efforts, offering more genomic insights into the spread of HPAI A/H5N1 and contributing valuable information for future prevention strategies. Full article
(This article belongs to the Special Issue H5N1 Influenza Viruses)
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18 pages, 4386 KiB  
Article
Progressive Adaptation of Subtype H6N1 Avian Influenza Virus in Taiwan Enhances Mammalian Infectivity, Pathogenicity, and Transmissibility
by Zuoyi Zheng, Xifeng Chen, Rutian Zheng, Zhigang Yan, Long Li, Rirong Chen, Lifeng Li, Yongmei Liu, Yi Guan and Huachen Zhu
Viruses 2025, 17(5), 733; https://doi.org/10.3390/v17050733 - 20 May 2025
Viewed by 28
Abstract
The interspecies transmission of avian influenza viruses remains a significant public health concern. H6 viruses have gained attention following the first human infection by a chicken-origin H6N1 virus (A/Taiwan/02/2013, Hu/13), highlighting their zoonotic potential. To understand the evolutionary trajectory and mammalian adaptation of [...] Read more.
The interspecies transmission of avian influenza viruses remains a significant public health concern. H6 viruses have gained attention following the first human infection by a chicken-origin H6N1 virus (A/Taiwan/02/2013, Hu/13), highlighting their zoonotic potential. To understand the evolutionary trajectory and mammalian adaptation of this Taiwan lineage, we compared two avian isolates (A/Chicken/Taiwan/CF19/2009, Ck/09; A/Chicken/Taiwan/2267/2012, Ck/12) and Hu/13 in vitro and in vivo. Hu/13 exhibited enhanced replication in MDCK cells, producing larger plaques and higher viral titers than Ck/09 and Ck/12. In BALB/c mice, Hu/13 demonstrated the highest pathogenicity and mortality, followed by Ck/12, while Ck/09 induced minimal morbidity. Hu/13 and Ck/12 replicated efficiently in respiratory tissues, eliciting robust cytokine responses and severe pulmonary lesions. In ferrets, Hu/13 showed relatively efficient transmission, infecting all direct physical-contact and two out of three airborne-contact ferrets, whereas Ck/09 failed to transmit. Histopathology confirmed escalating lung pathology from Ck/09 to Ck/12 and Hu/13. Whole-genome sequencing identified adaptive mutations in Hu/13 during ferret replication, though no canonical mammalian-adaptive changes (e.g., PB2-E627K or HA-Q226L) were detected. These findings demonstrate progressive mammalian adaptation, replication efficiency, and transmissibility within the Taiwan H6N1 lineage. Enhanced surveillance is crucial to monitor mammalian-adaptive mutations, informing pandemic preparedness and public health strategies. Full article
(This article belongs to the Special Issue Advances in Animal Influenza Virus Research: Third Edition)
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15 pages, 1837 KiB  
Article
Characterization of an Emerging Recombinant Duck Circovirus in Northern Vietnam, 2023–2024
by Hieu Van Dong, Dai Quang Trinh, Giang Huong Thi Tran, Thanh Thi Vu, Thinh Hung Ba Nguyen, Amonpun Rattanasrisomporn, Dao Anh Tran Bui and Jatuporn Rattanasrisomporn
Viruses 2025, 17(5), 732; https://doi.org/10.3390/v17050732 - 20 May 2025
Viewed by 32
Abstract
This study aimed to characterize the duck circovirus circulating in Northern Vietnam based on complete genome sequences. Between 2023 and 2025, 45 pooled tissue samples were collected from nine duck flocks in several provinces in Northern Vietnam. Of the 45 samples tested, 16 [...] Read more.
This study aimed to characterize the duck circovirus circulating in Northern Vietnam based on complete genome sequences. Between 2023 and 2025, 45 pooled tissue samples were collected from nine duck flocks in several provinces in Northern Vietnam. Of the 45 samples tested, 16 (35.56%) were positive for the DuCV genome, as determined using conventional polymerase chain reaction. Nine representative strains were selected for viral genome sequencing. The results indicated that the complete Vietnamese DuCV genomes were from 1992 to 1995 bp in length, and the degree of nucleotide identity shared among them ranged from 96.88% to 99.84%. Phylogenetic analysis of the complete genomes showed that the nine Vietnamese DuCV strains belonged to genotype I, subgenotypes Ia (two strains), Ib (four strains), and Ic (three strains). These viral strains were genetically related to viruses reported in China from 2019 to 2023. Recombination events occurred on the Cap gene sequences of three Vietnamese DuCV strains (Vietnam/VNUA-102/2023, Vietnam/VNUA-225/2023, and Vietnam/VNUA-318/2024). One positive selection was detected on the Rep protein sequence. Full article
(This article belongs to the Special Issue Animal Models in Emerging/Re-Emerging Infectious Diseases)
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14 pages, 770 KiB  
Article
Prevalence of Doravirine Resistance Mutations in a Large-Scale HIV-1 Transmitted Drug Resistance Survey in Buenos Aires, Argentina
by Diego Cecchini, Isabel Cassetti, Florencia Scarnato, Agustina Fiori, Jimena Nuevo, Clara Villaverde, Adriana Sucari, María C. Torroija, Emiliano Bissio, Gabriela Bugarin and Gustavo Lopardo
Viruses 2025, 17(5), 731; https://doi.org/10.3390/v17050731 - 20 May 2025
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Abstract
Background: Argentina has reported moderate to high levels of transmitted drug resistance in people living with HIV/AIDS (PLWHA), mostly to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Doravirine (DOR) has a unique resistance profile and retains potent antiviral activity in the presence of the most [...] Read more.
Background: Argentina has reported moderate to high levels of transmitted drug resistance in people living with HIV/AIDS (PLWHA), mostly to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Doravirine (DOR) has a unique resistance profile and retains potent antiviral activity in the presence of the most prevalent NNRTI-associated resistant viruses. Scarce data exist regarding the frequency of DOR resistance-associated mutations (RAMs) in Latin America. We describe the prevalence of DOR RAMs in samples from adults PLWHA in Buenos Aires, Argentina, in the context of a survey of transmitted drug resistance (TDR). Material and Methods: A cross-sectional study was undertaken utilizing samples collected between 2017 and 2021 at two reference HIV clinics. Samples were analyzed for RAMs using the World Health Organization (WHO) mutation list. Mutations to DOR were assessed with the Stanford and Agence Nationale de Recherches sur le SIDA (ANRS) algorithms. Rilpivirine (RPV) RAMs were assessed using the Stanford algorithm. Susceptibility to NNRTIs was evaluated using the HIVdb Program with Stanford and ANRS criteria. Results: Samples from 1667 PLWHA were analyzed: 81.2% were male, with 52.6% identifying as men who have sex with men. According to the WHO list, the overall TDR was 12.1% (n = 203). The prevalence of RAMs was 10.1% (170/1667) for NNRTIs, 4% (67/1667) for nucleoside reverse-transcriptase inhibitors (NRTIs), and 1.7% (30/1667) for protease inhibitors (PIs). The most frequent NNRTI mutations were K103N (5.6%), G190A (0.89%), and K103S (0.77%). The prevalence of DOR RAMs was <2%, with the most common being Y188L (0.53%). Rilpivirine RAM prevalence was 6%. Susceptibility to DOR, RPV, efavirenz, and nevirapine as given by the Stanford algorithm was 97.4%, 92%, 91.4%, and 90.4%, respectively. The ANRS criteria yielded susceptibility rates of 98.3%, 93.3%, 92.3%, and 90.8%, respectively. Regarding NRTIs, thymidine analog mutations (including T215 revertants) were the most frequent RAMs. Among PIs, the most prevalent RAMs were M46L (0.47%) and V82A (0.35%). Conclusions: Our study shows the persistence of moderate to high levels of resistance to first-generation NNRTIs. Despite this, prevalence was low for DOR. Surveillance of TDR remains critical for recommendations of ART initiation. Full article
(This article belongs to the Special Issue Viral Resistance)
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9 pages, 294 KiB  
Brief Report
Prevalence and Clinical Manifestation of Astrovirus Gastroenteritis in Adults: A Seven-Year Study in Washington D.C., USA
by Maryam Mehdipour Dalivand, Maher Ali and Rebecca Yee
Viruses 2025, 17(5), 730; https://doi.org/10.3390/v17050730 - 20 May 2025
Viewed by 37
Abstract
Gastroenteritis is commonly caused by viral etiologies. The inclusion of astrovirus on multiplex, syndromic gastrointestinal PCR panels allows for the detection and characterization of infected patients. This retrospective, observational, clinical study examines the epidemiology and clinical characteristics of astrovirus infections in adults from [...] Read more.
Gastroenteritis is commonly caused by viral etiologies. The inclusion of astrovirus on multiplex, syndromic gastrointestinal PCR panels allows for the detection and characterization of infected patients. This retrospective, observational, clinical study examines the epidemiology and clinical characteristics of astrovirus infections in adults from our institution in Washington D.C. (USA) over a seven-year period. Chart abstraction was performed to collect patient demographics, laboratory results, clinical presentation, and management. The overall positivity rate of astrovirus was 0.6%. Peak seasons were late winter to spring (February–April). The mean age was 32 years old (range: 18–52 years). All patients presented with gastroenteritis symptoms and were immunocompetent except one. Symptoms varied among diarrhea, abdominal pain, vomiting, and fever, but patients in age group 30–39 years experienced less vomiting (p = 0.01). Infected patients had an increase in monocytes and neutrophils and a decrease in lymphocytes (p < 0.001). Gastrointestinal co-infections were seen in 24% of our patients. In all patients, clinicians acknowledged the detection of astrovirus and discharged patients without further treatment. The median length of stay was 6 h, and no patients were admitted into the intensive care unit. We show that astrovirus infections in immunocompetent adults were associated with mild disease associated with specific cell counts and different symptoms correlated with age. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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14 pages, 2734 KiB  
Article
Isolation and Pathogenicity of a Natural Recombinant Pig Reproductive and Respiratory Syndrome Virus in Northeast China
by Zhixin Tian, Qiwei Li, Luxiang Xu, Dexin Liang, Yuan Li, Ziqi Shi, Lingzhi Luo, Jiechao Jin, Xiaoyi Huo, Xiumei Dong and Han Zhou
Viruses 2025, 17(5), 729; https://doi.org/10.3390/v17050729 - 19 May 2025
Viewed by 132
Abstract
First reported in 1987, the porcine reproductive and respiratory syndrome virus (PRRSV) has significantly disrupted the major regions affected by PRRSV in the pig breeding industry. Recently, outbreaks of disease caused by recombinant PRRSV strains in China have raised serious concerns. Effective immunization [...] Read more.
First reported in 1987, the porcine reproductive and respiratory syndrome virus (PRRSV) has significantly disrupted the major regions affected by PRRSV in the pig breeding industry. Recently, outbreaks of disease caused by recombinant PRRSV strains in China have raised serious concerns. Effective immunization and infection control in pig populations is critical, as the virus frequently undergoes mutation and recombination. This study characterized a novel recombinant PRRSV strain, BX/CH/22, isolated from Northeast China. Genetic analysis revealed that BX/CH/22 is a recombinant of JXA1, NADC 30-like, and NADC 34-like strains. Phylogenetic analysis of the non-structural protein (NSP) 2 region classified BX/CH/22 as JXA1 PRRSV-like, with a characteristic deletion of 30 discontinuous amino acids in NSP2. However, Open Reading Frame (ORF) 5 analysis classified it as NADC 30-like PPRSV, while whole-genome phylogenetic analysis classified it as NADC 34-like PPRSV. Recombination analysis revealed that BX/CH/22 contains an NADC 34-like PRRSV backbone, an NSP-coding region from NADC 30-like PRRSV, and an ORF2-ORF6 region from NADC 34-like PRRSV. The strain was isolated from serum samples obtained from commercial swine farms undergoing active PRRS outbreaks. In animal experiments, all BX/CH/22-challenged piglets exhibited persistent fever, with peak temperatures >40.5 °C at 4–9 dpi resolving by 11 dpi, accompanied by cough, anorexia, and lethargy. A significant reduction in daily weight gain was observed in infected groups compared to asymptomatic controls, with a 100% survival rate. Our findings provide early warning for PRRSV immune control strategies. Full article
(This article belongs to the Special Issue Porcine Viruses 2024)
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16 pages, 4545 KiB  
Article
Transcriptomic Analysis of the Spleen from Asian Seabass (Lates calcarifer) Infected with Infectious Spleen and Kidney Necrosis Virus
by Hong-Yi Xin, Lim Xin Ying, Lee Ching Pei Carmen and Mookkan Prabakaran
Viruses 2025, 17(5), 728; https://doi.org/10.3390/v17050728 - 19 May 2025
Viewed by 146
Abstract
Infectious spleen and kidney necrosis virus (ISKNV) is an emerging viral pathogen with an expanding host range, posing a significant threat to economically important fish species. In this study, we isolated the ISKNV strain responsible for disease outbreaks in Asian seabass (Lates [...] Read more.
Infectious spleen and kidney necrosis virus (ISKNV) is an emerging viral pathogen with an expanding host range, posing a significant threat to economically important fish species. In this study, we isolated the ISKNV strain responsible for disease outbreaks in Asian seabass (Lates calcarifer) and analyzed the transcriptomic profile of spleen tissues from experimentally infected fish. The phylogenetic analysis confirmed that the virus belongs to clade I of ISKNV. Next-generation sequencing identified differentially expressed genes, providing a comprehensive overview of the transcriptional landscape in the spleen of ISKNV-infected fish. The pathway analysis revealed complex host–virus interactions, impacting immune regulation, endocytosis, cell communication, cell cycle arrest, and programmed cell death. To further investigate these interactions, we analyzed relevant pathways in the Reactome database for Asian seabass, humans, and zebrafish, constructed a protein–protein interaction (PPI) network using STRING database, and identified hub genes using six different algorithms. This analysis revealed 69 key genes, including 41 hub genes and 28 key genes that connect different pathways or clusters within the PPI network. These findings provide new insights into the molecular mechanisms driving ISKNV infection in Asian seabass. Future research should focus on elucidating the regulatory functions of these key genes and their roles in ISKNV pathogenesis. Full article
(This article belongs to the Special Issue Iridoviruses, 2nd Edition)
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11 pages, 2000 KiB  
Article
HTLV-I Basic Leucine Zipper Factor (sHBZ) Actively Associates with Nucleophosmin (B23) in the Nucleolus
by Nahid Moghadam, Yong Xiao, Francois Dragon and Benoit Barbeau
Viruses 2025, 17(5), 727; https://doi.org/10.3390/v17050727 - 19 May 2025
Viewed by 126
Abstract
Human T cell leukemia virus type 1 (HTLV 1) is an oncogenic retrovirus responsible for the development of adult T cell leukemia (ATL). The minus strand of HTLV-1 provirus encodes an oncoprotein named HTLV-1 bZIP factor (HBZ), which plays a pivotal role in [...] Read more.
Human T cell leukemia virus type 1 (HTLV 1) is an oncogenic retrovirus responsible for the development of adult T cell leukemia (ATL). The minus strand of HTLV-1 provirus encodes an oncoprotein named HTLV-1 bZIP factor (HBZ), which plays a pivotal role in viral replication and T cell proliferation. Of particular interest is the spliced HBZ isoform (sHBZ), which is predominantly expressed in ATL cells and localizes within the nucleolus, conferring immortalizing properties to T cells. Our previous study has shown that sHBZ colocalizes and associates with Nucleophosmin/B23, a nucleolar phosphoprotein with multiple functions. In this study, through an optimized nucleolar isolation method, we first confirmed sHBZ’s nucleolar localization via Western blotting in transfected HEK293T cells, chronically HTLV-1-infected T cell lines, and freshly infected HeLa cells. We further demonstrated that the sHBZ/B23 association predominantly occurs in the nucleolus by co-immunoprecipitation of cell fractions. Our study highlights the nucleolar localization of sHBZ and its possibly essential interaction with this nucleolar-residing protein, leading to cell immortalization. Full article
(This article belongs to the Special Issue Virus-Host Protein Interactions)
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17 pages, 4115 KiB  
Article
Uncovering SARS-CoV-2 Molecular Epidemiology Across the Pandemic Transition: Insights into Transmission in Clinical and Environmental Samples
by Vrushali D. Patil, Rashmi Chowdhary, Anvita Gupta Malhotra, Jitendra Singh, Debasis Biswas, Rajnish Joshi and Jagat Rakesh Kanwar
Viruses 2025, 17(5), 726; https://doi.org/10.3390/v17050726 - 19 May 2025
Viewed by 220
Abstract
Background: Respiratory droplets are the main way in which the COVID-19 pandemic’s causal agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), spreads. Angiotensin-converting enzyme 2 (ACE2) receptors, especially in lung cells, allow the virus to enter host cells. However, ACE2 expression in intestinal cells [...] Read more.
Background: Respiratory droplets are the main way in which the COVID-19 pandemic’s causal agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), spreads. Angiotensin-converting enzyme 2 (ACE2) receptors, especially in lung cells, allow the virus to enter host cells. However, ACE2 expression in intestinal cells has sparked worries about possible fecal transfer, particularly in poor-sanitation areas like India. Methods: Between July 2021 and July 2024, clinical (nasopharyngeal, saliva, and stool samples) and sewage samples were collected from outpatient departments and sewage treatment plants (STPs), respectively, from the high-population-density area under study in order to investigate SARS-CoV-2 transmission. Results: This proof-of-concept study analyzed clinical samples from n = 60 COVID-19-positive patients at a central Indian tertiary care hospital and n = 156 samples from hospital STPs. Variants of SARS-CoV-2 were found using qRT-PCR and Next-Generation Sequencing (NGS). Of the n = 37 qRT-PCR-positive patients who gave their assent, 30% had stool samples that tested positive for viral RNA. In 70% of positive NP and 65% of positive saliva samples, along with two stool samples from immunocompromised patients, the live virus was identified using Vero E6 cell lines. Although 18% of the tests reported qRT-PCR-positive results, no live virus was detected in sewage samples despite NGS validation. The detection of SARS-CoV-2 in the absence of confirmed clinical cases may indicate the silent circulation of the virus within the community, suggesting that sewage surveillance can serve as an early warning system before an outbreak occurs. Conclusions: These findings provide critical insights into the importance of continuous environmental surveillance, silent virus circulation, changes in viral epidemiology throughout the years, and strategies to mitigate coronavirus outbreaks. Full article
(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 4th Edition)
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25 pages, 2300 KiB  
Article
Discovery and Genome Characterization of Three New Rhabdoviruses Infecting Passiflora spp. in Brazil
by Andreza Henrique Vidal, Ana Clara Rodrigues Abreu, Jorge Flávio Sousa Dantas-Filho, Monique Jacob Xavier Vianna, Cristiano Lacorte, Emanuel Felipe Medeiros Abreu, Gustavo Pereira Felix, Dione Mendes Teixeira Alves-Freitas, Bruna Pinheiro-Lima, Isadora Nogueira, Fabio Gelape Faleiro, Raul Castro Carriello Rosa, Onildo Nunes Jesus, Marcio Martinello Sanches, Yam Sousa Santos, Rosana Blawid, José Leonardo Santos Jiménez, Maite Freitas Silva Vaslin, Elliot Watanabe Kitajima, Magnolia de Araujo Campos, Rafaela Salgado Fontenele, Arvind Varsani, Fernando Lucas Melo and Simone Graça Ribeiroadd Show full author list remove Hide full author list
Viruses 2025, 17(5), 725; https://doi.org/10.3390/v17050725 - 19 May 2025
Viewed by 166
Abstract
This study aimed to explore the RNA viruses affecting Passiflora species in Brazil. Our results enhance the understanding of the viruses that infect Passiflora plants by identifying and characterizing three previously unrecognized viruses: Passiflora cytorhabdovirus (PFCV), Passiflora nucleorhabdovirus 1 (PaNV1), and Passiflora nucleorhabdovirus [...] Read more.
This study aimed to explore the RNA viruses affecting Passiflora species in Brazil. Our results enhance the understanding of the viruses that infect Passiflora plants by identifying and characterizing three previously unrecognized viruses: Passiflora cytorhabdovirus (PFCV), Passiflora nucleorhabdovirus 1 (PaNV1), and Passiflora nucleorhabdovirus 2 (PaNV2). These rhabdoviruses were identified through high-throughput sequencing and validated by reverse transcription-polymerase chain reaction (RT-PCR) in various Passiflora species. PFCV has a genome organization 3′-N-P-P3-P4-M-G-P7-L-5′ and was classified as a novel member of the Gammacytorhabdovirus genus. A particularly noteworthy feature of PFCV is its glycoprotein, as the genomes of other gammarhabdoviruses do not contain this gene. PFCV has a high incidence across multiple locations and was identified in plants from Northeastern, Central, and Southeastern Brazil. PaNV1 with genome structure 3′-N-P-P3-M-G-L-5′ and PaNV2 with genome organization 3′-N-X-P-Y-M-G-L-5′ are new members of the Alphanucleorhabdovirus genus and have a more restricted occurrence. Importantly, all three viruses were found in mixed infections alongside at least one other virus. In situ observations confirmed mixed infections, with PaNV2 particles co-located in tissues with a potyvirus and a carlavirus. Phylogenetic and glycoprotein sequence similarity network analysis provided insights into their evolutionary placement and potential vector associations. These findings expand the known diversity of rhabdoviruses in Passiflora and contribute to the understanding of their evolution and epidemiology. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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13 pages, 281 KiB  
Review
The Role of TDP-43 in SARS-CoV-2-Related Neurodegenerative Changes
by Dong-Hwi Kim, Jae-Hyeong Kim, Min-Tae Jeon, Kyu-Sung Kim, Do-Geun Kim and In-Soo Choi
Viruses 2025, 17(5), 724; https://doi.org/10.3390/v17050724 - 19 May 2025
Viewed by 134
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has been linked to long-term neurological effects with multifaceted complications of neurodegenerative diseases. Several studies have found that pathological changes in transactive response DNA-binding protein of 43 kDa (TDP-43) are involved in these cases. This review explores [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic has been linked to long-term neurological effects with multifaceted complications of neurodegenerative diseases. Several studies have found that pathological changes in transactive response DNA-binding protein of 43 kDa (TDP-43) are involved in these cases. This review explores the causal interactions between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and TDP-43 from multiple perspectives. Some viral proteins of SARS-CoV-2 have been shown to induce pathological changes in TDP-43 through its cleavage, aggregation, and mislocalization. SARS-CoV-2 infection can cause liquid−liquid phase separation and stress granule formation, which accelerate the condensation of TDP-43, resulting in host RNA metabolism disruption. TDP-43 has been proposed to interact with SARS-CoV-2 RNA, though its role in viral replication remains to be fully elucidated. This interaction potentially facilitates viral replication, while viral-induced oxidative stress and protease activity accelerate TDP-43 pathology. Evidence from both clinical and experimental studies indicates that SARS-CoV-2 infection may contribute to long-term neurological sequelae, including amyotrophic lateral sclerosis-like and frontotemporal dementia-like features, as well as increased phosphorylated TDP-43 deposition in the central nervous system. Biomarker studies further support the link between TDP-43 dysregulation and neurological complications of long-term effects of COVID-19 (long COVID). In this review, we presented a novel integrative framework of TDP-43 pathology, bridging a gap between SARS-CoV-2 infection and mechanisms of neurodegeneration. These findings underscore the need for further research to clarify the TDP-43-related neurodegeneration underlying SARS-CoV-2 infection and to develop therapeutic strategies aimed at mitigating long-term neurological effects in patients with long COVID. Full article
(This article belongs to the Section Coronaviruses)
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13 pages, 15467 KiB  
Article
Evaluating Neutralizing Antibodies in Hantavirus-Infected Patients Using Authentic Virus and Recombinant Vesicular Stomatitis Virus Systems
by Punya Shrivastava-Ranjan, Jamie A. Kelly, Laura K. McMullan, Deborah Cannon, Laura Morgan, Payel Chatterjee, Shilpi Jain, Joel M. Montgomery, Mike Flint, César G. Albariño and Christina F. Spiropoulou
Viruses 2025, 17(5), 723; https://doi.org/10.3390/v17050723 - 19 May 2025
Viewed by 162
Abstract
Hantaviruses, including the Sin Nombre virus (SNV) and Andes virus (ANDV), are associated with severe global health risks, causing high mortality rates in hantavirus pulmonary syndrome (HPS) patients. Neutralizing antibodies are essential for virus clearance and survival, making neutralization assays critical for understanding [...] Read more.
Hantaviruses, including the Sin Nombre virus (SNV) and Andes virus (ANDV), are associated with severe global health risks, causing high mortality rates in hantavirus pulmonary syndrome (HPS) patients. Neutralizing antibodies are essential for virus clearance and survival, making neutralization assays critical for understanding immunity and evaluating therapeutic strategies. In this study, we developed a recombinant vesicular stomatitis virus (VSV)-based surrogate system expressing SNV and ANDV glycoproteins (GPCs), enabling neutralization studies under biosafety level 2 conditions. The neutralization titers obtained with the VSV-based system closely matched the findings from authentic hantavirus assays performed under biosafety level 3 conditions, confirming its potential as a useful tool for determining immune responses and advancing hantavirus research. Full article
(This article belongs to the Special Issue Hantavirus 2024)
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17 pages, 2391 KiB  
Review
Evolution of Antiviral Drug Resistance in SARS-CoV-2
by Roy Dinata, Piyush Baindara and Santi M. Mandal
Viruses 2025, 17(5), 722; https://doi.org/10.3390/v17050722 - 18 May 2025
Viewed by 248
Abstract
The COVID-19 pandemic has had a significant impact and continues to alarm the entire world due to the rapid emergence of new variants, even after mass vaccinations. There is still an urgent need for new antivirals or strategies to combat the SARS-CoV-2 infections; [...] Read more.
The COVID-19 pandemic has had a significant impact and continues to alarm the entire world due to the rapid emergence of new variants, even after mass vaccinations. There is still an urgent need for new antivirals or strategies to combat the SARS-CoV-2 infections; however, we have success stories with nirmatrelvir. Drug repurposing and drug discovery may lead to a successful SARS-CoV-2 antiviral; however, rapid drug use may cause unexpected mutations and antiviral drug resistance. Conversely, novel variants of the SARS-CoV-2 can diminish the neutralizing efficacy of vaccines, thereby enhancing viral fitness and increasing the likelihood of drug resistance emergence. Additionally, the disposal of antivirals in wastewater also contributes to drug resistance. Overall, the present review summarizes the strategies and mechanisms involved in the development of drug resistance in SARS-CoV-2. Understanding the mechanism of antiviral resistance is crucial to mitigate the significant healthcare threat and to develop effective therapeutics against drug resistance. Full article
(This article belongs to the Special Issue Mechanism of Receptor Recognition in Coronavirus, 2nd Edition)
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14 pages, 7209 KiB  
Article
Establishment and Implementation of the Point-of-Care RT-RAA-CRISPR/Cas13a Diagnostic Test for Foot-And-Mouth Disease Virus Serotype O in Pigs
by Ping Meng, Bo Ni, Chenyu Li, Zhou Sha, Chunju Liu, Weijie Ren, Rong Wei, Fuxiao Liu, Jinming Li and Zhiliang Wang
Viruses 2025, 17(5), 721; https://doi.org/10.3390/v17050721 - 17 May 2025
Viewed by 211
Abstract
Foot and mouth disease virus (FMDV) is a highly pathogenic virus that mainly infects cloven hooved animals, such as pigs. The establishment of a rapid, sensitive and accurate point-of-care detection method is critical for the timely identification and elimination of infected pigs for [...] Read more.
Foot and mouth disease virus (FMDV) is a highly pathogenic virus that mainly infects cloven hooved animals, such as pigs. The establishment of a rapid, sensitive and accurate point-of-care detection method is critical for the timely identification and elimination of infected pigs for controlling this disease. In this study, a RT-RAA-CRISPR/Cas13a method was developed for the detection of FMDV serotype O in pigs. Six pairs of RT-RAA primers were designed based on the conserved gene sequence of FMDV serotype O, and the optimal amplification primers and reaction temperatures were screened. The CRISPR-derived RNA (crRNA) was further designed based on the optimal target band sequence and the most efficient crRNA was screened. The results revealed that FMDV-O-F4/R4 was the optimal primer set, and the optimal temperature for the RT-RAA reaction was 37 °C. Moreover, crRNA4 exhibited the strongest detection signal among the six crRNAs. The established RT-RAA-CRISPR/Cas13a method demonstrated high specificity and no cross-reactivity with other common swine pathogens such as Senecavirus A (SVA), porcine reproductive and respiratory virus (PRRSV), porcine epidemic diarrhea virus (PEDV), porcine circovirus type 2 (PCV2), classical swine fever virus (CSFV), and pseudorabies virus (PRV), additionally, it was observed to be highly sensitive, with a detection limit of 19.1 copies/µL. The repeatability of this method was also observed to be good. This method could produce stable fluorescence and exhibited good repeatability when three independent experiments yielded the same results. A validation test using three types of simulated clinical samples (including swab, tissue, and serum samples) revealed a 100% concordance rate. The detection results could be visualized via a fluorescence reader or lateral flow strips (LFSs). Thus, a highly specific and sensitive RT-RAA-CRISPR/Cas13a detection method was developed and is expected to be applied for the rapid detection of FMDV serotype O in situ. Full article
(This article belongs to the Special Issue Advances in Endemic and Emerging Viral Diseases in Livestock)
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12 pages, 388 KiB  
Article
Foscarnet Versus Ganciclovir for Severe Congenital Cytomegalovirus Infection: Short- and Long-Term Follow-Up
by Giovanni Nigro, Marta Buzzi, Milena Catenaro, Eleonora Coclite and Mario Muselli
Viruses 2025, 17(5), 720; https://doi.org/10.3390/v17050720 - 17 May 2025
Viewed by 140
Abstract
Background: Cytomegalovirus (CMV) infection is the most common and serious congenital infection, with universal screening in pregnancy, standardized therapy, and a vaccine still lacking. Study design: In the 1990s, we noted that intravenous ganciclovir did not cure some children with severe sequelae due [...] Read more.
Background: Cytomegalovirus (CMV) infection is the most common and serious congenital infection, with universal screening in pregnancy, standardized therapy, and a vaccine still lacking. Study design: In the 1990s, we noted that intravenous ganciclovir did not cure some children with severe sequelae due to congenital cytomegalovirus (CMV) infection. Therefore, we performed an open randomized trial using intravenous foscarnet as an alternative to intravenous ganciclovir in 24 infants (12 in each therapy group), all with severe neurological manifestations due to congenital CMV infection. Nine and five infants, belonging to the foscarnet or ganciclovir group, respectively, had abnormal hearing. One infant in each group also had chorioretinitis. Concomitantly, 12 CMV-infected infants with similar manifestations, who did not receive any therapy, were used as controls. The results of short-term (2 years) and long-term (7–29 years, mean 22.2) follow-up are reported herein. Short-term results: Neurological outcomes were normal in five of the twelve children who were treated with foscarnet, compared to nine of the twelve children given ganciclovir. None of the untreated children were healthy. There was a statistically significant difference (p = 0.023) between the treated and untreated children. Hearing was normal in four of the twelve children treated with foscarnet, seven of the twelve children treated with ganciclovir, and two untreated children. Long-term-results: Two children in both therapy groups died before the age of 17 years, and six untreated children died between 7 and 26 years of age. Neurological outcomes were normal in three of the ten children treated with foscarnet, in two of the ten treated with ganciclovir, and in none of the untreated children. Hearing was normal in two children treated with foscarnet, in six children treated with ganciclovir, and in one untreated child. Conclusions: Intravenous ganciclovir and foscarnet were found to be safe at long-term follow-up and appeared to be capable of mitigating the neurological and auditory consequences of congenital CMV disease at the short-term follow-up. However, there was progressive worsening of the symptomatology in all three groups, with a statistically significant increase in the number of deaths (p = 0.035) among 4 of the 24 children in the therapy groups and 6 of the 12 untreated children. Full article
(This article belongs to the Special Issue Congenital Cytomegalovirus Infection: Volume II)
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15 pages, 2900 KiB  
Article
Characterization of Papillomatous Lesions and Genetic Diversity of Bovine Papillomavirus from the Amazon Region
by Fernanda dos Anjos Souza, Cíntia Daudt, André de Medeiros Costa Lins, Igor Ribeiro dos Santos, Lorena Yanet Cáceres Tomaya, Agnes de Souza Lima, Eduardo Mitke Brandão Reis, Rafael Augusto Satrapa, David Driemeier, Audrey Bagon, Cláudio Wageck Canal, Felipe Masiero Salvarani and Flavio Roberto Chaves da Silva
Viruses 2025, 17(5), 719; https://doi.org/10.3390/v17050719 (registering DOI) - 16 May 2025
Viewed by 86
Abstract
Bovine papillomaviruses (BPVs) have been widely characterized from cutaneous warts in cattle worldwide. However, there are still limited studies addressing the geographic distribution of viral types and their potential associations with the histopathological characteristics of lesions, particularly in the vast and ecologically diverse [...] Read more.
Bovine papillomaviruses (BPVs) have been widely characterized from cutaneous warts in cattle worldwide. However, there are still limited studies addressing the geographic distribution of viral types and their potential associations with the histopathological characteristics of lesions, particularly in the vast and ecologically diverse Amazon region. This study aimed to histologically and phylogenetically characterize cutaneous papillomatous lesions in cattle from the Vale do Guaporé, located in the Brazilian Western Amazon. A total of 54 wart samples were collected from 44 cattle clinically diagnosed with cutaneous papillomatosis. Histopathological analysis classified 58.33% of cases as fibropapillomas and 39.58% as squamous papillomas. Molecular analysis, based on L1 gene amplification and sequencing, identified the presence of previously reported BPV types (BPV2, 4, 5, 12, 13, and 15), along with a novel BPV14 subtype and three putative new types (PNT). Statistical analysis revealed that BPV2 was significantly associated with fibropapillomas (p = 0.023), whereas BPV13 was linked to cauliflower-like morphological lesions (p = 0.008). These findings enhance the understanding of BPV diversity circulating in cattle from the Amazon region and provide valuable insights into the clinicopathological aspects of bovine cutaneous papillomatosis, which may aid in future epidemiological surveillance and disease control strategies. Full article
(This article belongs to the Special Issue Advances in Endemic and Emerging Viral Diseases in Livestock)
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10 pages, 1308 KiB  
Article
Assessing Urban Yellow Fever Transmission Risk: Aedes aegypti Vector Competence in Argentina
by Estefanía R. Boaglio, Evangelina Muttis, Mariel Feroci, Cintia Fabbri, Graciela Minardi, Juliana Sánchez, María V. Micieli and Silvina Goenaga
Viruses 2025, 17(5), 718; https://doi.org/10.3390/v17050718 - 16 May 2025
Viewed by 73
Abstract
Yellow fever is a viral disease with historical importance since epidemics caused thousands of deaths at the end of the 19th century in Argentina. That event was associated with the presence of Aedes aegypti. After the mosquito eradication in South America in [...] Read more.
Yellow fever is a viral disease with historical importance since epidemics caused thousands of deaths at the end of the 19th century in Argentina. That event was associated with the presence of Aedes aegypti. After the mosquito eradication in South America in the 1960–1970 decade, no epidemic was detected related to this species but epizootics have occurred due to sylvatic vectors belonging to Haemagogus and Sabethes genera. Due to the recolonization of Ae. aegypti and its expanded distribution, the risk of the urbanization of yellow fever has increased over time. However, the reasons why the urban cycle of the yellow fever virus (YFV) has not occurred in South America so far are unknown. We explore the vector competence of Ae. aegypti for YFV transmission. The mosquitos evaluated belonged to colonies from center and northwest cities from Argentina, taking into account the particular genetic features of this mosquito species detected in this country from 2016. We used a viral strain originally isolated in 2009 from Sabethes albiprivus in the country. Viral infection in mosquito body, legs, and saliva was evaluated to estimate the rates of infection, dissemination, and transmission. Our results indicate that both mosquito colonies are competent vectors in the transmission of the YFV but with differences between them. Regarding the infection timeline, we observed a very early infection in the La Plata colony at 3 DPI in contrast to previous studies. This research improves our understanding of the risks of urban YFV transmission in Argentina, highlighting the need for surveillance and specialized vector control strategies in urban settings to prevent yellow fever outbreaks. Full article
(This article belongs to the Special Issue Recent Advances on Arboviruses Pathogenesis and Evolution)
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11 pages, 2256 KiB  
Article
Novel Orthohantavirus Associated with Hantavirus Pulmonary Syndrome in Northern Argentina
by Carla M. Bellomo, Sebastian Kehl, Daniel Oscar Alonso, Walter López, Flavia Cassinelli, Rocío María Coelho, Gabriela Bravo, Sara Aguirre, Marcela Dib, Natalia Periolo, Concepción Toscano, José Gil, Francisco García Campos, Ignacio Ferro and Valeria Paula Martinez
Viruses 2025, 17(5), 717; https://doi.org/10.3390/v17050717 - 16 May 2025
Viewed by 429
Abstract
In this work, we performed the genetic characterization of a new variant of orthohantavirus associated with a fatal case of hantavirus pulmonary syndrome, outside the known endemic region, in northwestern Argentina. We first confirmed an orthohantavirus infection by ELISA, testing for the detection [...] Read more.
In this work, we performed the genetic characterization of a new variant of orthohantavirus associated with a fatal case of hantavirus pulmonary syndrome, outside the known endemic region, in northwestern Argentina. We first confirmed an orthohantavirus infection by ELISA, testing for the detection of IgM and IgG antibodies. Then, we extracted RNA from 100 microliters of serum, the only sample available, followed by RT-PCR. The amplicons were sequenced using Sanger and next-generation sequencing technology. We obtained partial sequences of 1253 bp, 799 bp and 1675 bp from the S-, M- and L-segments, respectively, showing low sequence identities with all the previously characterized hantaviruses (10.9%, 13.5% and 15.1% of the divergence, respectively). The phylogenetic analysis showed that this virus belongs to the Orthohantavirus andesense species (ANDV), and among the ANDV-like variants, it is more closely related to the Lechiguanas clade. Similar percentages of divergence were considered sufficient to distinguish AND-like variants in previous works. As the patient had no travel history before the onset of disease was reported, we conducted rodent surveys to confirm the presence of reservoirs. The rodent assemblage was compatible with the transitional zone among different ecoregions (Yungas, Chaco and Monte). Moreover, one of the species captured, Oligoryzomys flavescens, was previously described as a reservoir of hantavirus. This species may either host several variants across its range or encompass a species complex, as proposed by some authors. Full article
(This article belongs to the Special Issue Hantavirus 2024)
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16 pages, 1604 KiB  
Article
Comparison of Three Commercial ELISA Kits for Detection of Antibodies Against SARS-CoV-2 in Serum Samples from Different Animal Species
by Leira Fernández-Bastit, Sílvia Marfil, Edwards Pradenas, Julià Blanco, Júlia Vergara-Alert and Joaquim Segalés
Viruses 2025, 17(5), 716; https://doi.org/10.3390/v17050716 - 16 May 2025
Viewed by 99
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 19 (COVID-19) pandemic, significantly impacting global health, economies, and social stability. In February 2020, the first cases of SARS-CoV-2 infections in animals were documented, highlighting the potential risks posed by regular [...] Read more.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 19 (COVID-19) pandemic, significantly impacting global health, economies, and social stability. In February 2020, the first cases of SARS-CoV-2 infections in animals were documented, highlighting the potential risks posed by regular human–animal interactions in facilitating viral transmission. In consequence, it is essential to validate surveillance methods for SARS-CoV-2 in animals. In the present study, 101 sera from different animal species (36 cats, 41 dogs, 4 ferrets, 10 wild boar, 6 domestic goats, and 4 lions) were tested using three different ELISA kits to evaluate humoral responses against SARS-CoV-2. ELISA results were compared and correlated with a pseudovirus neutralization test (pVNT), considered as the reference assay. ELISA-1, targeting the receptor binding domain (RBD) neutralizing antibodies (nAbs) of SARS-CoV-2, exhibited the highest diagnostic performance, and proved to be a reliable tool for initial screenings in high-throughput animal studies. In contrast, ELISA-2 (also targeting RBD nAbs) and ELISA-3 (targeting nucleoprotein antibodies) demonstrated lower sensitivity for detecting seropositive animals. Full article
(This article belongs to the Section Animal Viruses)
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17 pages, 2540 KiB  
Review
Adaptor Protein Complexes in HIV-1 Pathogenesis: Mechanisms and Therapeutic Potential
by Maria Elena Barone, Alexis Lim, Madison Woody, Parisa Taklifi, Fatema Yeasmin, Kequan Wang, Mary K. Lewinski, Rajendra Singh, Charlotte A. Stoneham, Xiaofei Jia and John Guatelli
Viruses 2025, 17(5), 715; https://doi.org/10.3390/v17050715 - 16 May 2025
Viewed by 369
Abstract
Adaptor protein (AP) complexes are critical components of the cellular membrane transport machinery. They mediate cargo selection during endocytosis and intracellular vesicular trafficking. Five AP complexes have been characterized (AP1-5), and together their roles extend to diverse cellular processes including the homeostasis of [...] Read more.
Adaptor protein (AP) complexes are critical components of the cellular membrane transport machinery. They mediate cargo selection during endocytosis and intracellular vesicular trafficking. Five AP complexes have been characterized (AP1-5), and together their roles extend to diverse cellular processes including the homeostasis of membranous organelles, membrane protein turnover, and immune responses. Human Immunodeficiency Virus type 1 (HIV-1) and other lentiviruses co-opt these complexes to support immune evasion and the assembly of maximally infectious particles. HIV-1 Nef interacts with AP1 and AP2 to manipulate intracellular trafficking and downregulate immune-related proteins such as CD4 and MHC-I. Vpu also co-opts AP1 and AP2, modulating the innate defense protein BST2 (Tetherin) and facilitating the release of virions from infected cells. The envelope glycoprotein (Env) hijacks AP complexes to reduce its expression at the cell surface and potentially support incorporation into virus particles. Some data suggest that Gag co-opts AP3 to drive assembly at intracellular compartments. In principle, targeting the molecular interfaces between HIV-1 proteins and AP complexes is a promising therapeutic approach. Blocking these interactions should impair HIV-1’s ability to produce infectious particles and evade immune defenses, leading to novel antivirals and facilitating a cure. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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18 pages, 1457 KiB  
Article
HIV–HPV Co-Infection and Identification of Novel High-Risk HPV Among Women at Two Hospital Centers in Cotonou, Republic of Benin
by Clémence D. Gouton, Ifeoluwa O. Bejide, Oludayo O. Ope-ewe, Marius Adjagba, Simon Azonbakin, Gaonyadiwe Muzanywa, Florence T. Akinyi, Arnaud Agbanlinsou, Yanique Goussanou, Onikepe Folarin, Anatole Laleye, Christian T. Happi and Chinedu A. Ugwu
Viruses 2025, 17(5), 714; https://doi.org/10.3390/v17050714 - 16 May 2025
Viewed by 338
Abstract
Persistent high-risk human papillomaviruses (HR-HPVs) infection is the leading cause of cervical cancer. With over 200 circulating genotypes, HPV detection, management, and prevention remain challenging. In Benin, HPV prevalence and genotype distribution are largely unknown, and no national HPV vaccination program exists. This [...] Read more.
Persistent high-risk human papillomaviruses (HR-HPVs) infection is the leading cause of cervical cancer. With over 200 circulating genotypes, HPV detection, management, and prevention remain challenging. In Benin, HPV prevalence and genotype distribution are largely unknown, and no national HPV vaccination program exists. This study investigates the prevalence, genotypic diversity, and risk factors of HIV–HPV co-infection among women in Cotonou, Benin. Cervical swabs were collected from 100 women living with HIV (WLWHIV) and 51 women without HIV (WWHIV) at two hospitals. DNA extraction and nested polymerase chain reaction (PCR) were used to detect HPV, followed by Sanger sequencing for genotyping. Chi-squared analysis was used to assess risk factors. HPV was detected in 85% (85/100) of WLWHIV and 60.8% (31/51) of WWHIV (p = 0.002), confirming HIV as an independent risk factor. Fifteen HR-HPV genotypes were identified, with HPV 45 most prevalent in WLWHIV and HPV 16 in WWHIV. Notably, HR-HPV 67, 70, and 82 were detected for the first time in Benin. Unmarried status and detectable HIV load were significant risk factors for co-infection. The high HPV prevalence, particularly among WLWHIV, underscores the urgent need for HPV surveillance and vaccination in Benin. Identifying novel HR-HPV genotypes highlights the necessity for ongoing monitoring and targeted prevention strategies. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Clinical Manifestations of Persistent Viral Infections)
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15 pages, 10579 KiB  
Article
Infectious Spleen and Kidney Necrosis Virus Triggers Ferroptosis in CPB Cells to Enhance Virus Replication
by Qiushuang Zhang, Ouqin Chang, Qiang Lin, Hongru Liang, Yinjie Niu, Xia Luo, Baofu Ma, Ningqiu Li and Xiaozhe Fu
Viruses 2025, 17(5), 713; https://doi.org/10.3390/v17050713 - 16 May 2025
Viewed by 82
Abstract
The role of ferroptosis—a novel iron-dependent programmed cell death pathway—in infectious spleen and kidney necrosis virus (ISKNV) infection remains poorly understood. Here, we demonstrate that ISKNV infection induces ferroptosis in CPB cells. Following ISKNV challenge, CPB cells exhibited hallmark morphological alterations including mitochondrial [...] Read more.
The role of ferroptosis—a novel iron-dependent programmed cell death pathway—in infectious spleen and kidney necrosis virus (ISKNV) infection remains poorly understood. Here, we demonstrate that ISKNV infection induces ferroptosis in CPB cells. Following ISKNV challenge, CPB cells exhibited hallmark morphological alterations including mitochondrial shrinkage, increased membrane density, and cristae reduction. Biochemical assays confirmed significant time-dependent elevations in ferroptosis markers: malondialdehyde (MDA, 1.7-fold), reactive oxygen species (ROS, 3.14-fold), and ferrous iron (Fe2+, 1.42-fold) compared to controls (p < 0.05). Mechanistic studies revealed that ISKNV downregulated glutathione peroxidase 4 (GPx4) while upregulating acyl-CoA synthetase long-chain family member 4 (ACSL4), as validated by quantitative real-time PCR (qRT-PCR) and immunoblotting. Ferroptosis induction with erastin enhanced ISKNV replication, whereas inhibition with liproxstatin-1 suppressed viral yield. These findings establish that ISKNV exploits ferroptosis to facilitate its replication, and pharmacological blockade of this pathway significantly suppresses viral propagation, providing a new strategy and intervention approach for controlling ISKNV infection. Full article
(This article belongs to the Special Issue Aquatic Animal Viruses and Antiviral Immunity)
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21 pages, 312 KiB  
Review
Update: Immunotherapeutic Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma
by Fangdi Sun and A. Dimitrios Colevas
Viruses 2025, 17(5), 712; https://doi.org/10.3390/v17050712 - 16 May 2025
Viewed by 144
Abstract
The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased substantially over the past three decades, and since 2017, it has been recognized in the AJCC staging system as distinct from its HPV-negative counterpart. The underlying mechanisms of HPV-associated carcinogenesis, [...] Read more.
The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased substantially over the past three decades, and since 2017, it has been recognized in the AJCC staging system as distinct from its HPV-negative counterpart. The underlying mechanisms of HPV-associated carcinogenesis, tumor microenvironment, and host immune response represent opportunities for therapeutic development. While anti-PD-1 immunotherapy is now part of standard treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in general, there are no established immunotherapeutic strategies specifically for HPV-related HNSCC. In this context, multiple emerging approaches are being actively studied—among these are therapeutic vaccines with or without anti-PD-(L)1 adjuvants, peptide–HLA-based immunotherapeutic platforms, and adoptive cell therapies including tumor-infiltrating lymphocytes (TILs), T-cell receptor (TCR) therapy, and chimeric antigen receptor (CAR) T-cell therapy. Beyond further maturation of these novel immunotherapeutic strategies, additional work is needed to delineate the optimal disease state of application (localized versus recurrent/metastatic), as well as in the development of small molecule inhibitors targeting HPV-specific mechanisms of viral oncogenesis. Full article
(This article belongs to the Special Issue Advancements in Immunotherapy for Human Papillomavirus)
14 pages, 1502 KiB  
Article
Genetic Diversity in the Capsid Protein-Coding Region of HIV-1 Circulating in Benguela, Angola: Implications for Primary Resistance to the Novel Capsid Inhibitor Lenacapavir
by Gonçalo Queirós, Lesya Yefimenko, Filomena M. Pereira and João Piedade
Viruses 2025, 17(5), 711; https://doi.org/10.3390/v17050711 - 16 May 2025
Viewed by 73
Abstract
In 2023, the HIV-1 pandemic claimed around 630,000 lives worldwide due to AIDS-related complications. Its burden is significantly heavier in Sub-Saharan Africa, where an increased HIV-1 genetic diversity is common, which increases the risk of resistance to antiretroviral (ARV) drugs. This study aims [...] Read more.
In 2023, the HIV-1 pandemic claimed around 630,000 lives worldwide due to AIDS-related complications. Its burden is significantly heavier in Sub-Saharan Africa, where an increased HIV-1 genetic diversity is common, which increases the risk of resistance to antiretroviral (ARV) drugs. This study aims to update the molecular epidemiology of HIV-1 in Angola, focusing specifically on the gag gene, which is often overlooked, and to assess the potential viability of lenacapavir (LEN)-based ARV therapy in the region. A total of 243 blood samples were collected from ARV-naïve, HIV-infected patients at the General Hospital of Benguela, city of Benguela, Angola. The capsid-encoding region of HIV-1 proviral DNA was amplified by PCR and sequenced. Phylogenetic analysis was performed using the maximum likelihood method, and genome recombinant forms were characterised through bootscanning analysis. Primary resistance mutations to LEN were identified using Stanford University’s HIVdb algorithm. Among the 80 successfully sequenced samples, 13 different genetic forms/subtypes were identified, with unique recombinant forms (URFs) (37.5%, 30/80) and subtype C (31.25%, 25/80) being the most prevalent. Regarding resistance mutations, none were detected, apart from four polymorphic mutations. These findings reinforce Angola’s position as a transitional HIV-1 hotspot between the genetically highly diverse Central Africa and the subtype C-dominated Southern Africa, while also supporting the potential effectiveness of LEN-based regimens for treatment and prevention of HIV-1 infections in the future. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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12 pages, 4621 KiB  
Article
Detection of a New Recombinant Rabbit Hemorrhagic Disease Virus 2 in China and Development of Virus-like Particle-Based Vaccine
by Bo Hu, Wenyu Dong, Yanhua Song, Zhiyu Fan, Patrizia Cavadini and Fang Wang
Viruses 2025, 17(5), 710; https://doi.org/10.3390/v17050710 - 16 May 2025
Viewed by 92
Abstract
Rabbit hemorrhagic disease virus (RHDV) is a very virulent virus of the genus Lagovirus causing severe and fatal hepatitis in the European rabbit (Oryctolagus cuniculus). RHDV has two distinct genotypes: GI.1 (RHDV) and GI.2 (RHDV2). The first RHDV2/GI.2 strain was identified [...] Read more.
Rabbit hemorrhagic disease virus (RHDV) is a very virulent virus of the genus Lagovirus causing severe and fatal hepatitis in the European rabbit (Oryctolagus cuniculus). RHDV has two distinct genotypes: GI.1 (RHDV) and GI.2 (RHDV2). The first RHDV2/GI.2 strain was identified as a recombinant virus between a non-pathogenic (GI.3P) and a pathogenic (GI.2) lagovirus, and the recombination is thought to have been a key mechanism in the emergence and evolution of RHDV2. Here, a new variant of RHDV2 was identified affecting domestic rabbits on Chinese farms, with a mortality rate of 70–80%. Phylogenetic analysis indicated that the nonstructural portion of this newly identified strain’s genome clustered with the GI.1a variants. In contrast, the capsid gene shared the highest nucleotide identity of 97.9% with the North American GI.2 strains, suggesting a possible introduction in China of North American strains and recombination with the GI.1a strains circulating in China. We have produced a recombinant vaccine using the first Chinese GI.2 strain, SC2020/0401, by cloning the vp60 gene into a baculovirus expression vector. Virus-like particles (VLPs) were then produced in Sf9 insect cells, and a challenge study was performed. Rabbits immunized with the VLP vaccine survived 7 d after being challenged with the new virus. The results indicate that commercial vaccines are urgently required in China to control the circulation of RHDV2 variants. Full article
(This article belongs to the Section Animal Viruses)
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19 pages, 2727 KiB  
Article
Single Amino Acid Residue W33 of tva Receptor Is Critical for Viral Entry and High-Affinity Binding of Avian Leukosis Virus Subgroup K
by Eliška Gáliková, David Přikryl, Salomé Prost, Dana Kučerová, Kateřina Trejbalová and Jiří Hejnar
Viruses 2025, 17(5), 709; https://doi.org/10.3390/v17050709 - 15 May 2025
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Abstract
Avian leukosis virus (ALV), the prototypical alpharetrovirus, causes tumorigenesis, immunosuppression, and wasting disease in poultry. The ALV genus is classified into ten subgroups, which differ in their host range, cell tropism, and receptor usage. The subgroups A, B, K, and J cause significant [...] Read more.
Avian leukosis virus (ALV), the prototypical alpharetrovirus, causes tumorigenesis, immunosuppression, and wasting disease in poultry. The ALV genus is classified into ten subgroups, which differ in their host range, cell tropism, and receptor usage. The subgroups A, B, K, and J cause significant economic losses worldwide. The most recently discovered subgroup, ALV-K, which is now widespread in China, has been shown to use the tva cell receptor and share it with ALV-A. However, the specific amino acid residues crucial for ALV-K host cell entry remain unknown. Using precise tva expression and chimeric tva receptors, we further elucidated the significance of the cysteine-rich domain in mediating interactions with both ALV-A and ALV-K. Through a comprehensive analysis of mutated tva receptor variants, we pinpointed tryptophan at position 33 (W33) as a pivotal amino acid residue essential for ALV-K virus binding and entry. Of note is the finding that the substitution of W33 induced resistance to ALV-K while preserving sensitivity to ALV-A. This study not only represents an advance in the understanding of the specificity of the tva receptor for ALV-K, but also offers a biotechnological strategy for the prevention of ALV-K infections in poultry. Full article
(This article belongs to the Section Animal Viruses)
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25 pages, 3117 KiB  
Article
Postnatal Epigenetic Alterations in Calves Persistently Infected with Bovine Viral Diarrhea Virus
by Jessica N. Kincade, Dilyara A. Murtazina, Hanah M. Georges, Carolina L. Gonzalez-Berrios, Jeanette V. Bishop, Terry E. Engle, Marcela Henao-Tamayo, Jordan M. Eder, Erin M. McDonald, Darcy M. Deines, Brie M. Wright, Hana Van Campen and Thomas R. Hansen
Viruses 2025, 17(5), 708; https://doi.org/10.3390/v17050708 - 15 May 2025
Viewed by 191
Abstract
Bovine viral diarrhea virus (BVDV) is a globally prevalent pathogen causing severe detriment to the cattle industry. Vertical infection occurring before the development of the fetal adaptive immune response, before 125 days of gestation, results in an immunotolerant, persistently infected (PI) calf. It [...] Read more.
Bovine viral diarrhea virus (BVDV) is a globally prevalent pathogen causing severe detriment to the cattle industry. Vertical infection occurring before the development of the fetal adaptive immune response, before 125 days of gestation, results in an immunotolerant, persistently infected (PI) calf. It was hypothesized that epigenetic alterations observed in the splenic tissue of PI fetuses at gestational day 245 would persist into the postnatal period. White blood cell DNA from five PI and five control heifers at 4 months of age was subjected to reduced representation bisulfite sequencing and interpreted within the context of complete blood count and flow cytometry data herein. Analysis revealed 8367 differentially methylated sites contained within genes associated with the immune and cardiac system, as well as hematopoiesis. Differences observed in the complete blood counts of PI heifers include increased monocytes, microcytic anemia, and elevated platelets with decreased mean platelet volume. Flow cytometry revealed increased classical monocytes, B cells, and CD4+/CD8B+ and CD25+/CD127− T cells, as well as decreased γδ+, CD4+, and CD4−/CD8B− T cells. Investigation of the PI methylome provides a new perspective on the mechanisms of pathologies and provides potential biomarkers for the rapid identification of PI cattle. Full article
(This article belongs to the Special Issue Bovine Viral Diarrhea Viruses and Other Pestiviruses)
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