Viruses

14 pages, 330 KiB

Open AccessArticle

Beyond Crisis Response: A Roundtable on Long-Term Strategies for Managing African Swine Fever

by Lisa Rogoll, Katja Schulz, Jana Schulz, Jonas Brock and Hans-Hermann Thulke

Viruses 2025, 17(5), 604; https://doi.org/10.3390/v17050604 - 23 Apr 2025

Today, African swine fever (ASF) continues to spread in European wild boar populations, while existing management strategies respond to an animal health emergency. The current disease scenario, characterised by constant re-emergence and persistence of infection, poses a fundamental social problem for the future [...] Read more.

Today, African swine fever (ASF) continues to spread in European wild boar populations, while existing management strategies respond to an animal health emergency. The current disease scenario, characterised by constant re-emergence and persistence of infection, poses a fundamental social problem for the future of ASF policy in the affected regions. A World Café workshop was organised with veterinary epidemiology experts from practice, academia and governance. The aim was to explore the problems caused by ASF in Germany for the various stakeholders and to gather perspectives for the long-term management of ASF. The panel of experts linked the unintended extension of the animal health emergency concept to the tensions between the various stakeholders and the risk of system fatigue. Sustainable management approaches need to balance rapid response to outbreaks with long-term management efforts. The experts emphasised the importance of risk-based strategies, stakeholder involvement and evidence-based policies in ASF management. The expert panel also highlighted the need for transparent communication to increase public trust and acceptance. The need for more flexible approaches requires a more open discussion about the intractable challenges posed by the long-term presence of ASF, the adequacy of existing regulations and possible visions for the future. Full article

(This article belongs to the Collection African Swine Fever Virus (ASFV))

12 pages, 2667 KiB

Open AccessBrief Report

Deletion of the African Swine Fever Virus Gen I196L in the Georgia2010 Isolate Genome Does Not Affect Virus Replication or Virulence in Domestic Pigs

by Elizabeth Ramirez-Medina, Paul A. Azzinaro, Alyssa Valladares, Ediane Silva, Leeanna Burton, Leandro Sastre, Vivian O’Donnell, James J. Zhu, Douglas P. Gladue and Manuel V. Borca

Viruses 2025, 17(5), 603; https://doi.org/10.3390/v17050603 - 23 Apr 2025

Abstract

African swine fever (ASF) is a lethal disease of domestic pigs that is currently challenging swine production in large areas of Eurasia and the Caribbean. The causative agent, ASF virus (ASFV), is a large, double-stranded, and structurally complex virus. The ASFV genome encodes [...] Read more.

African swine fever (ASF) is a lethal disease of domestic pigs that is currently challenging swine production in large areas of Eurasia and the Caribbean. The causative agent, ASF virus (ASFV), is a large, double-stranded, and structurally complex virus. The ASFV genome encodes for more than 160 proteins; however, the functions of most of them are still in the process of being characterized. Recently, ASFV gene I196L has been reported as being critically involved in disease production in domestic pigs. We report here that a recombinant virus derived from the Georgia 2010 isolate (ASFV-G) lacking the I196L gene, ASFV-G-∆I196L, had the same ability to replicate in primary cultures of swine macrophage and, when experimentally inoculated in pigs, produced a fatal form of the disease similar to that caused by the parental virulent ASFV-G. Therefore, deletion of the I196L gene does not significantly affect virus replication and virulence in domestic pigs of the ASFV Georgia 2010 isolate. Full article

(This article belongs to the Collection African Swine Fever Virus (ASFV))

18 pages, 8229 KiB

Open AccessArticle

Investigation of HCPro-Mediated Ethylene Synthesis Pathway Through RNA-seq Approaches

by Xinpeng Jiang, Lan Dong, Renjing Wan, Changli Zeng and Ting Yang

Viruses 2025, 17(5), 602; https://doi.org/10.3390/v17050602 - 23 Apr 2025

Abstract

Chilli veinal mottle virus (ChiVMV) severely compromises the quality and yield of solanaceous crops. The helper component protease (HCPro) of ChiVMV functions as a multifunctional RNA silencing suppressor that subverts host antiviral defenses through diverse strategies, However, the underlying mechanisms remain mechanistically unresolved. [...] Read more.

Chilli veinal mottle virus (ChiVMV) severely compromises the quality and yield of solanaceous crops. The helper component protease (HCPro) of ChiVMV functions as a multifunctional RNA silencing suppressor that subverts host antiviral defenses through diverse strategies, However, the underlying mechanisms remain mechanistically unresolved. In this study, HCPro-overexpressing (HCPro-OX) and wild-type (WT) plants were inoculated with ChiVMV to monitor the physiological and molecular changes. Transcriptome analysis identified 11,815 differentially expressed genes (DEGs) under viral infection, among which 1115 genes were specifically regulated by HCPro. KEGG enrichment analysis revealed that the DEGs were significantly associated with plant hormone signal transduction pathways, indicating their crucial role in host–virus interactions. Furthermore, functional clustering of HCPro-regulated DEGs specifically identified key components in ethylene biosynthesis pathways. GO analysis of DEGs between virus-inoculated WT and HCPro-OX plants annotated ethylene biosynthesis-related genes NtACO and NtACS. qPCR validation confirmed that the expression of ethylene biosynthesis-related genes was suppressed by HCPro. Exogenous treatments with the ethylene precursor ACC demonstrated that ethylene suppressed viral accumulation, enhanced POD activity, and reduced the ROS accumulation induced by viral infection. In conclusion, our results demonstrate that HCPro promotes viral infection by suppressing ethylene biosynthesis, which in turn attenuates peroxidase activity, leading to ROS accumulation. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

7 pages, 4012 KiB

Open AccessEditorial

Novel Antiviral Agents: Synthesis, Molecular Modelling Studies and Biological Investigation, 2nd Edition

by Simone Brogi

Viruses 2025, 17(5), 601; https://doi.org/10.3390/v17050601 - 23 Apr 2025

Abstract

After the success of the Special Issue entitled “Novel Antiviral Agents: Synthesis, Molecular Modelling Studies and Biological Investigation” (https://www [...] Full article

(This article belongs to the Special Issue Novel Antiviral Agents: Synthesis, Molecular Modelling Studies and Biological Investigation, 2nd Edition)

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33 pages, 1847 KiB

Open AccessReview

Immunological Control of Herpes Simplex Virus Type 1 Infection: A Non-Thermal Plasma-Based Approach

by Julia Sutter, Jennifer L. Hope, Brian Wigdahl, Vandana Miller and Fred C. Krebs

Viruses 2025, 17(5), 600; https://doi.org/10.3390/v17050600 - 23 Apr 2025

Abstract

Herpes simplex virus type 1 (HSV-1) causes a lifelong infection due to latency established in the trigeminal ganglia, which is the source of recurrent outbreaks of cold sores. The lifelong persistence of HSV-1 is further facilitated by the lack of cure strategies, unsuccessful [...] Read more.

Herpes simplex virus type 1 (HSV-1) causes a lifelong infection due to latency established in the trigeminal ganglia, which is the source of recurrent outbreaks of cold sores. The lifelong persistence of HSV-1 is further facilitated by the lack of cure strategies, unsuccessful vaccine development, and the inability of the host immune system to clear HSV-1. Despite the inefficiencies of the immune system, the course of HSV-1 infection remains under strict immunological control. Specifically, HSV-1 is controlled by a CD8⁺ T cell response that is cytotoxic to HSV-1-infected cells, restricts acute infection, and uses noncytolytic mechanisms to suppress reactivation in the TG. When this CD8⁺ T cell response is disrupted, reactivation of latent HSV-1 occurs. With antiviral therapies unable to cure HSV-1 and prophylactic vaccine strategies failing to stimulate a protective response, we propose non-thermal plasma (NTP) as a potential therapy effective against recurrent HSV-1 infection. We have demonstrated that NTP, when applied directly to HSV-1-infected cells, has antiviral effects and stimulates cellular stress and immunomodulatory responses. We further propose that the direct effects of NTP will lead to long-lasting indirect effects such as reduced viral seeding into the TG and enhanced HSV-1-specific CD8⁺ T cell responses that exert greater immune control over HSV-1 infection. Full article

(This article belongs to the Special Issue Herpesviruses and Associated Diseases)

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35 pages, 395 KiB

Open AccessReview

Treating Adenovirus Infection in Transplant Populations: Therapeutic Options Beyond Cidofovir?

by Niyati Narsana, David Ha and Dora Y. Ho

Viruses 2025, 17(5), 599; https://doi.org/10.3390/v17050599 - 23 Apr 2025

Abstract

Adenovirus (AdV) infections can lead to significant morbidity and increased mortality in immunocompromised populations such as hematopoietic stem cell and solid organ transplant recipients. This review evaluates currently available and emerging therapies for AdV infections. Cidofovir, while most commonly used, is limited by [...] Read more.

Adenovirus (AdV) infections can lead to significant morbidity and increased mortality in immunocompromised populations such as hematopoietic stem cell and solid organ transplant recipients. This review evaluates currently available and emerging therapies for AdV infections. Cidofovir, while most commonly used, is limited by its variable efficacy and nephrotoxicity. This led to the development of brincidofovir, which has a better safety profile and great in vitro potency against AdV. The use of ribavirin and ganciclovir has been reported in the literature, but their use is limited due to inconsistent efficacy. Immune-based approaches, such as adoptive T-cell therapy, have shown promise in achieving viral clearance and improving survival but remain constrained by challenges related to manufacturing complexity and risks of graft-versus-host disease. This review underscores the need for standardized treatment protocols as well as comparative studies to identify optimal dosing and timing to initiate treatment. Future research should focus on individualized treatment approaches and the development of novel therapeutic agents to address the unmet clinical needs of AdV management. Full article

(This article belongs to the Special Issue Viral Infections in Immunocompromised Hosts)

18 pages, 3055 KiB

Open AccessArticle

Stromal Interferon Regulatory Factor 3 Can Antagonize Human Papillomavirus Replication by Supporting Epithelial-to-Mesenchymal Transition

by Oluwamuyiwa T. Amusan, Rebecca Lopez, Elijah Burks, Jessica Trammel, Gaurav Raikhy, Hongyan Guo and Jason Bodily

Viruses 2025, 17(5), 598; https://doi.org/10.3390/v17050598 - 23 Apr 2025

Abstract

Epithelia contribute to the innate immune system through barrier formation and through signaling to immune cells. When the barrier is breached, epithelial cells undergo epithelial-to-mesenchymal transition (EMT) as part of the wound healing process. EMT is largely directed by signals from the stromal [...] Read more.

Epithelia contribute to the innate immune system through barrier formation and through signaling to immune cells. When the barrier is breached, epithelial cells undergo epithelial-to-mesenchymal transition (EMT) as part of the wound healing process. EMT is largely directed by signals from the stromal microenvironment, including transforming growth factor beta (TGFβ1), and antagonizes normal epithelial differentiation. How EMT and innate immunity may be connected molecularly has not been explored, although both processes are likely to occur simultaneously. Keratinocytes are the host cell type for human papillomaviruses (HPV), which can induce EMT in certain conditions but also depend on differentiation for their replication. We previously found that the innate immune factor interferon regulatory factor 3 (IRF3) inhibits epithelial differentiation and reduces the expression of HPV16 late genes. Here we report that IRF3 in the stroma compartment promotes an EMT-like pattern of gene expression in an HPV16-containing epithelium. The depletion of stromal IRF3 resulted in the downregulation of TGFβ1-related signaling in both the stroma and epithelium. IRF3 binds to the TGFB1 promoter in human foreskin fibroblasts and is necessary for TGFB1 mRNA production. Because an EMT-like state is unfavorable for differentiation-dependent HPV16, we observed that all EMT markers examined were reduced in the presence of episomal HPV16. Together, we show that stromal IRF3 can disrupt epithelial differentiation and act as an anti-HPV factor through the regulation of EMT, linking wound healing and immunity. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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27 pages, 4886 KiB

Open AccessArticle

A Novel Toolkit of SARS-CoV-2 Sub-Genomic Replicons for Efficient Antiviral Screening

by Maximilian Erdmann, Peter A. C. Wing, Isobel Webb, Maia Kavanagh Williamson, Tuksin Jearanaiwitayakul, Edward Sullivan, James Bazire, Iart Luca Shytaj, Jane A. McKeating, David A. Matthews and Andrew D. Davidson

Viruses 2025, 17(5), 597; https://doi.org/10.3390/v17050597 - 23 Apr 2025

Abstract

SARS-CoV-2 is classified as a containment level 3 (CL3) pathogen, limiting research access and antiviral testing. To address this, we developed a non-infectious viral surrogate system using reverse genetics to generate sub-genomic replicons. These replicons contained the nsp1 mutations K164A and H165A and [...] Read more.

SARS-CoV-2 is classified as a containment level 3 (CL3) pathogen, limiting research access and antiviral testing. To address this, we developed a non-infectious viral surrogate system using reverse genetics to generate sub-genomic replicons. These replicons contained the nsp1 mutations K164A and H165A and had the spike, membrane, ORF6, and ORF7a coding sequences replaced with various reporter and selectable marker genes. Replicons based on the ancestral Wuhan Hu-1 strain and the Delta variant of concern were replication-competent in multiple cell lines, as assessed by Renilla luciferase activity, fluorescence, immunofluorescence staining, and single-molecule fluorescent in situ hybridization. Antiviral assays using transient replicon expression showed that remdesivir effectively inhibited both replicon and viral replication. Ritonavir and cobicistat inhibited Delta variant replicons similarly to wild-type virus but did not inhibit Wuhan Hu-1 replicon replication. To further investigate the impact of nsp1 mutations, we generated a recombinant SARS-CoV-2 virus carrying the K164A and H165A mutations. The virus exhibited attenuated replication across a range of mammalian cell lines, was restricted by the type I interferon response, and showed reduced cytopathic effects. These findings highlight the utility of sub-genomic replicons as reliable CL2-compatible surrogates for studying SARS-CoV-2 replication and drug activity mechanisms. Full article

(This article belongs to the Special Issue Coronaviruses Pathogenesis, Immunity, and Antivirals (2nd Edition))

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8 pages, 2215 KiB

Open AccessBrief Report

Genetic and Antiviral Potential Characterization of Four Insect-Specific Viruses Identified and Isolated from Mosquitoes in Yunnan Province

by Qinxuan Miao, Lulu Deng, Xiang Le, Qian Li, Yuting Ning, Yimeng Duan, Qi Liu, Yinzhu Tao, Binghui Wang and Xueshan Xia

Viruses 2025, 17(5), 596; https://doi.org/10.3390/v17050596 - 23 Apr 2025

Abstract

Mosquitoes, comprising over 300 species, are pivotal vectors for transmitting arthropod-borne viruses (arboviruses) to vertebrates via bites, posing a significant public health threat with approximately 700,000 annual deaths. In contrast, insect-specific viruses (ISVs) exclusively infect insects and have no direct impact on human [...] Read more.

Mosquitoes, comprising over 300 species, are pivotal vectors for transmitting arthropod-borne viruses (arboviruses) to vertebrates via bites, posing a significant public health threat with approximately 700,000 annual deaths. In contrast, insect-specific viruses (ISVs) exclusively infect insects and have no direct impact on human health. Yunnan Province in China, located in tropical and subtropical regions, provides an ideal environment for mosquito habitation and has the highest diversity of known mosquito-borne viruses. In this study, mosquito samples were collected from eight cities and states in Yunnan Province, totaling 15,099 specimens. Based on the collection sites and mosquito species, the samples were divided into 110 groups for virus isolation. Four insect-specific viruses (Tanay virus [TANV], Culex orthoflavivirus [CxFV], Aedes orthoflavivirus [AeFV], La Tina virus [LTNV]) were successfully isolated, and co-infection studies with dengue virus (DENV-2) were conducted in C6/36 cells. Preliminary results suggested that these four insect-specific viruses may reduce the viral titer of DENV-2 in C6/36 cells. Understanding the intricate interactions between insect-specific viruses and mosquito-borne viruses is crucial for elucidating the multifaceted role of mosquitoes in arboviral transmission dynamics. Insect-specific viruses exhibit considerable potential as innovative biocontrol agents, with promising capacity to attenuate mosquito-borne viral transmission through the targeted modulation of mosquito innate immunity and physiological adaptations. Full article

(This article belongs to the Special Issue Zoonotic Viral Diseases: Drivers, Causes, Prevention and Cure, 2nd Edition)

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7 pages, 498 KiB

Open AccessCase Report

Interplay of Belatacept Immunosuppression and Maribavir Antiviral Activity in Recurrent CMV Viremia: Clinical Implications and Literature Review

by Imran Gani, Ahmad Mirza and Usman Baig

Viruses 2025, 17(5), 595; https://doi.org/10.3390/v17050595 - 23 Apr 2025

Abstract

Belatacept is a recombinant fusion protein used in renal transplant recipients, particularly when side effects from standard immunosuppressants occur. It offers a superior renal safety profile and is associated with better long-term renal graft outcomes. However, belatacept has been linked to atypical presentations [...] Read more.

Belatacept is a recombinant fusion protein used in renal transplant recipients, particularly when side effects from standard immunosuppressants occur. It offers a superior renal safety profile and is associated with better long-term renal graft outcomes. However, belatacept has been linked to atypical presentations of cytomegalovirus (CMV) infections, characterized by a prolonged and unpredictable course of viremia. We report a case involving a middle-aged African American female who developed acute kidney injury while on tacrolimus and was subsequently switched to belatacept. During treatment with belatacept, she experienced persistent and erratic CMV viremia lasting 58 weeks. The viremia showed an incomplete response to first-line antiviral therapy with valganciclovir, and the use of the novel antiviral agent maribavir also failed to achieve long-lasting viremic clearance. The resolution of the viremia was ultimately achieved only after discontinuing belatacept while continuing maribavir therapy. This case and literature review underscores the need for clinicians to remain vigilant for atypical CMV infections in renal transplant recipients treated with belatacept. If the complete clearance of viremia cannot be achieved despite the use of different antiviral agents, consideration should be given to modifying immunosuppressive therapy. Full article

(This article belongs to the Special Issue Immune Modulation by Human Cytomegalovirus)

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20 pages, 3205 KiB

Open AccessArticle

Hsa-miR-7974 Suppresses Epstein-Barr Virus Reactivation by Directly Targeting BZLF1 and BRLF1

by Haotian Li, Hui Wang, Jiao Wang, Xuexin Lu, Jieqiong Zhang, Mingming Wang, Dongbo Yu, Ying Li and Shiwen Wang

Viruses 2025, 17(5), 594; https://doi.org/10.3390/v17050594 - 23 Apr 2025

Abstract

Epstein-Barr virus (EBV) reactivation, a key factor in Epstein-Barr virus (EBV)-associated malignancies, is regulated by specific cellular microRNAs (miRNAs). This study investigated the role of Hsa-miR-7974 (miR-7974) in this process. miRNA sequencing revealed significant downregulation of miR-7974 in reactivated EBV-positive cell lines (Raji [...] Read more.

Epstein-Barr virus (EBV) reactivation, a key factor in Epstein-Barr virus (EBV)-associated malignancies, is regulated by specific cellular microRNAs (miRNAs). This study investigated the role of Hsa-miR-7974 (miR-7974) in this process. miRNA sequencing revealed significant downregulation of miR-7974 in reactivated EBV-positive cell lines (Raji and C666-1). Bioinformatics prediction and dual-luciferase assays confirmed the direct targeting of the EBV immediate-early gene BRLF1 by miR-7974. Furthermore, miR-7974 mimics suppressed, whereas inhibitors increased, the expression of key EBV lytic genes (BZLF1, BRLF1, and BMRF1) and the viral load, as validated by RT-qPCR. Bioinformatics analyses revealed the involvement of miR-7974 in cellular pathways such as membrane dynamics and signal transduction (MAPK, NF-κB, and IL-10), and its association with Hodgkin’s lymphoma, leukemia, and nasopharyngeal neoplasms. These findings establish that miR-7974 functions as a crucial negative regulator of EBV reactivation by directly targeting BRLF1, highlighting its potential significance in the pathogenesis of EBV-associated malignancies. Full article

(This article belongs to the Special Issue EBV and Disease: New Perspectives in the Post COVID-19 Era)

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14 pages, 3234 KiB

Open AccessArticle

Establishment and Evaluation of Fatigue Mice Model in the Convalescence Phase of Influenza A

by Xiaoke Zeng, Cheng Zhang, Jianing Shi, Xuan Ji, Keying Wang, Ling Li and Qinghu He

Viruses 2025, 17(5), 593; https://doi.org/10.3390/v17050593 - 22 Apr 2025

Abstract

Certain strains of Influenza A virus (IAV), a primary cause of influenza, can lead to pneumonia. Patients recovering from influenza pneumonia may experience physical discomfort akin to post-acute sequelae of COVID-19 (PASC). Despite extensive clinical research on viral pneumonia during convalescence, animal model [...] Read more.

Certain strains of Influenza A virus (IAV), a primary cause of influenza, can lead to pneumonia. Patients recovering from influenza pneumonia may experience physical discomfort akin to post-acute sequelae of COVID-19 (PASC). Despite extensive clinical research on viral pneumonia during convalescence, animal model studies are scarce, highlighting the need for a reliable model for pharmaceutical research. In this study, BALB/c mice were divided into three groups: NC (control), MC (infected with IAV), and Model (treated with oseltamivir post-infection for five days). A fatigue model was then induced in the Model group through diet restriction and weight-bearing swimming. The results showed the MC group had a 75% survival rate, while the NC and Model groups had 100%. Both the MC and Model groups experienced rapid weight loss followed by gradual recovery, differing significantly from the NC group. From dpi (days post-inoculation) 6 to dpi9, the MC group lost more weight than the NC group. The MC group had the highest pulmonary index, but there was no significant difference in IAV Nucleoprotein (NP) expression across groups. The Model group had higher IL-10 levels than the NC and MC groups, while the MC group had the highest TNF-α expression. Hematoxylin and eosin (H&E) staining revealed pathological changes in the MC and Model groups, with severe damage and pulmonary fibrosis in the MC group. Oxidative stress markers showed the MC group had the highest lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels and lowest superoxide dismutase (SOD) activity. Electron microscopy indicated mitochondrial damage in both the MC and Model groups. The Model group had the lowest splenic and thymic indices, with histological findings showing larger splenic nodules in the MC group and poor thymocyte density and atrophy in the Model group. The successful creation of this mouse model of influenza pneumonia convalescence phase fatigue, exhibiting fatigue syndrome with various symptoms, holds significance for PASC and other viral pneumonia convalescence phase animal model research. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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21 pages, 21040 KiB

Open AccessArticle

Lassa Virus Infection of Primary Human Airway Epithelial Cells

by Helena Müller-Kräuter, Sarah Katharina Fehling, Lucie Sauerhering, Birthe Ehlert, Janine Koepke, Juliane Schilling, Mikhail Matrosovich, Andrea Maisner and Thomas Strecker

Viruses 2025, 17(5), 592; https://doi.org/10.3390/v17050592 - 22 Apr 2025

Abstract

Lassa mammarenavirus (LASV), a member of the family Arenaviridae, is a highly pathogenic virus capable of causing severe systemic infections in humans. The primary host reservoir is the Natal multimammate mouse (Mastomys natalensis), with human infections typically occurring through mucosal exposure [...] Read more.

Lassa mammarenavirus (LASV), a member of the family Arenaviridae, is a highly pathogenic virus capable of causing severe systemic infections in humans. The primary host reservoir is the Natal multimammate mouse (Mastomys natalensis), with human infections typically occurring through mucosal exposure to virus-containing aerosols from rodent excretions. To better understand the molecular mechanisms underlying LASV replication in the respiratory tract, we utilized differentiated primary human airway epithelial cells (HAECs) grown under air–liquid interface conditions, closely mimicking the bronchial epithelium in vivo. Our findings demonstrate that HAECs are permissive to LASV infection and support productive virus replication. While LASV entry into polarized HAECs occurred through both apical and basolateral surfaces, progeny virus particles were predominantly released from the apical surface, consistent with an intrinsic apical localization of the envelope glycoprotein GP. This suggests that apical virus shedding from infected bronchial epithelia may facilitate LASV transmission via airway secretions. Notably, limited basolateral release at later stages of infection was associated with LASV-induced rearrangement of the actin cytoskeleton, resulting in compromised epithelial barrier integrity. Finally, we demonstrate that LASV-infected HAECs exhibited a pronounced type III interferon response. A detailed understanding of LASV replication and host epithelial responses in the respiratory tract could facilitate the development of targeted future therapeutics. Full article

(This article belongs to the Special Issue Viral Infection in Airway Epithelial Cells)

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17 pages, 2271 KiB

Open AccessArticle

Persistent Infections in Tick Cell Lines: The Role of Viral-Derived DNA Forms in Hazara Virus Replication and Cellular Survival

by Eva Dias, Filipe Tomaz, Silvia Fabi, Cristiano Salata, Ana Domingos and Gonçalo Seixas

Viruses 2025, 17(5), 591; https://doi.org/10.3390/v17050591 - 22 Apr 2025

Abstract

Crimean–Congo hemorrhagic fever virus (CCHFV) causes severe or fatal infections in humans and is geographically widespread. The virus has coevolved with its tick vectors, establishing persistent infections critical to its transmission. This study explored the mechanisms underpinning these persistent infections, using tick cell [...] Read more.

Crimean–Congo hemorrhagic fever virus (CCHFV) causes severe or fatal infections in humans and is geographically widespread. The virus has coevolved with its tick vectors, establishing persistent infections critical to its transmission. This study explored the mechanisms underpinning these persistent infections, using tick cell lines and the Hazara virus (HAZV) as a biosafety level 2 (BSL-2) model for CCHFV. Initially, an RT-qPCR protocol was developed to detect HAZV in tick cells. The study then focused on the production of virus-derived DNA (vDNAs) by tick cells as a defensive response to infection. These vDNAs regulate viral particle production, enabling tick cells to maintain viability and establish persistent infections. The experiments characterized vDNAs production, viral titers, and subcellular localization, and they examined the effect of the reverse transcriptase inhibitor azidothymidine triphosphate (AZT). The results showed that all tested tick cell lines supported HAZV replication, achieving persistent infections without cytopathic effects. vDNAs was detected in both the cytoplasm and nucleus, and its formation was dependent on HAZV infection. Importantly, vDNAs presence was linked to infection persistence; cells treated with AZT exhibited a marked reduction in vDNAs production and an associated increase in viral particle production, which correlated with higher cell death. These findings underscore the critical role of vDNAs in balancing viral replication and promoting long-term cell survival in tick cells, highlighting their importance in the coevolution of tick-borne viruses and their vectors. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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16 pages, 654 KiB

Open AccessArticle

Serologic Surveillance for Orthoflaviviruses and Chikungunya Virus in Bats and Opossums in Chiapas, Mexico

by J. Manuel Aranda-Coello, Carlos Machain-Williams, Manuel Weber, Alma R. Dzul Rosado, Tyler R. Simpkins and Bradley J. Blitvich

Viruses 2025, 17(5), 590; https://doi.org/10.3390/v17050590 - 22 Apr 2025

Abstract

We performed serologic surveillance for selected arthropod-borne viruses (arboviruses) in bats and opossums in the Lacandona Rainforest, Chiapas, Mexico, in 2023–2024. Sera were collected from 94 bats of at least 15 species and 43 opossums of three species. The sera were assayed by [...] Read more.

We performed serologic surveillance for selected arthropod-borne viruses (arboviruses) in bats and opossums in the Lacandona Rainforest, Chiapas, Mexico, in 2023–2024. Sera were collected from 94 bats of at least 15 species and 43 opossums of three species. The sera were assayed by the plaque reduction neutralization test (PRNT) for antibodies to eight orthoflaviviruses (dengue viruses 1–4, St. Louis encephalitis virus, T’Ho virus, West Nile virus, and Zika virus) and one alphavirus (chikungunya virus; CHIKV). Twelve (12.8%) bats and 15 (34.9%) opossums contained orthoflavivirus-specific antibodies. One bat (a Jamaican fruit bat) was seropositive for Zika virus, and 11 bats contained antibodies to an undetermined orthoflavivirus, as did the 15 opossums. All bats and most opossums seropositive for an undetermined orthoflavivirus had low PRNT titers, possibly because they had been infected with another (perhaps unrecognized) orthoflavivirus not included in the PRNTs. Antibodies that neutralized CHIKV were detected in three (7.0%) opossums and none of the bats. The three opossums had low CHIKV PRNT titers, and therefore, another alphavirus may have been responsible for the infections. In summary, we report serologic evidence of arbovirus infections in bats and opossums in Chiapas, Mexico. Full article

(This article belongs to the Section Animal Viruses)

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36 pages, 11357 KiB

Open AccessArticle

A Modular Mathematical Model of the Immune Response for Investigating the Pathogenesis of Infectious Diseases

by Maxim I. Miroshnichenko, Fedor A. Kolpakov and Ilya R. Akberdin

Viruses 2025, 17(5), 589; https://doi.org/10.3390/v17050589 - 22 Apr 2025

Abstract

The COVID-19 pandemic highlighted the importance of mathematical modeling for understanding viral infection dynamics and accelerated its application into immunological research. Collaborative efforts among international research groups yielded a wealth of experimental data, which facilitated model development and validation. This study focuses on [...] Read more.

The COVID-19 pandemic highlighted the importance of mathematical modeling for understanding viral infection dynamics and accelerated its application into immunological research. Collaborative efforts among international research groups yielded a wealth of experimental data, which facilitated model development and validation. This study focuses on developing a modular mathematical model of the immune response, capturing the interactions between innate and adaptive immunity, with an application to SARS-CoV-2 infection. The model was validated using experimental data from middle-aged individuals with moderate COVID-19 progression, including measurements of viral load in the upper and lower airways, serum antibodies, CD4+ and CD8+ T cells, and interleukin-6 levels. Parameter optimization and sensitivity analysis were performed to improve the model accuracy. Additionally, identifiability analysis was conducted to assess whether the data were sufficient for reliable parameter estimation. The verified model simulates the dynamics of moderate, severe, and critical COVID-19 progressions using measured data on lung epithelium damage, viral load, and IL-6 levels as key indicators of disease severity. We also performed a series of validation scenarios to assess whether the model correctly reproduces biologically relevant behaviors under various conditions, such as immunity hyperactivation, co-infection with HIV, and interferon administration as a therapeutic strategy. The model was developed as a component of the Digital Twin project and represents a general immune module that integrates both innate and adaptive immunity. It can be utilized for further COVID-19 research or serve as a foundation for studying other infectious diseases, provided sufficient data are available. Full article

(This article belongs to the Special Issue Computational Biology of Viruses: From Molecules to Epidemics, Volume 2)

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Viruses, Volume 17, Issue 5 (May 2025) – 16 articles

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