Viruses

10 pages, 1050 KiB

Open AccessArticle

Identification of the Emerging C1-like Lineage of Enterovirus A71 in Two Uruguayan Children with Hand-Foot-and-Mouth Disease and Neurological Complications

by Andrés Lizasoain, Natalia Martínez, Carla de Mora, Edivia Rodríguez, Nathalie Ledezma and Rodney Colina

Viruses 2024, 16(11), 1752; https://doi.org/10.3390/v16111752 - 8 Nov 2024

Abstract

Enterovirus A71 (EV-A71) is a major cause of hand-foot-and-mouth disease (HFMD), particularly in cases that involve complications affecting the nervous system or cardiopulmonary function. In South America, EV-A71 has primarily been identified through studies of acute flaccid paralysis (AFP) and other neurological disorders. [...] Read more.

Enterovirus A71 (EV-A71) is a major cause of hand-foot-and-mouth disease (HFMD), particularly in cases that involve complications affecting the nervous system or cardiopulmonary function. In South America, EV-A71 has primarily been identified through studies of acute flaccid paralysis (AFP) and other neurological disorders. In September 2022, two children from a small city in Uruguay were hospitalized with presumptive rhombencephalitis, exhibiting symptoms of HFMD. EV-A71 was identified through RT-PCR and next-generation sequencing of stool and skin lesion samples. A maximum-likelihood phylogenetic analysis of the P1 coding region classified the Uruguayan strains as part of an emerging lineage, primarily reported in Europe over the past decade, known as the C1-like lineage. The findings presented here represent the first detection of the EV-A71 C1-like lineage in cases of HFMD and encephalitis reported from South America, underscoring the urgent need to enhance surveillance for HFMD, aseptic meningitis, encephalitis, and AFP, in countries facing challenges in establishing effective surveillance programs related to enteroviruses and associated diseases. Full article

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

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12 pages, 1565 KiB

Open AccessArticle

Prevalence, Characteristics, and Distribution of Human Papillomavirus According to Age and HIV Status in Women of Eastern Cape Province, South Africa

by Zizipho Z. A. Mbulawa, Sinazo Kondlo, Sinalo Toni, Lindiwe M. Faye and Charles B. Businge

Viruses 2024, 16(11), 1751; https://doi.org/10.3390/v16111751 - 8 Nov 2024

Abstract

Human papillomavirus (HPV) is a sexually transmitted infection associated with the development of cervical cancer. This study investigated cervical HPV prevalence, characteristics, and distribution according to age and human immunodeficiency virus (HIV) status among women attending a public community health facility in the [...] Read more.

Human papillomavirus (HPV) is a sexually transmitted infection associated with the development of cervical cancer. This study investigated cervical HPV prevalence, characteristics, and distribution according to age and human immunodeficiency virus (HIV) status among women attending a public community health facility in the Eastern Cape Province of South Africa. A total of 325 participants (aged 18 to 60) visiting a community health facility for any reason were recruited. Cervical HPV infection was detected using the Seegene Anyplex™ II HPV28 assay (Seegene Inc., Seoul, South Korea). Overall HPV prevalence was 65.2% (95% CI: 59.9–70.2%), with the highest prevalence of 80.9% (95% CI: 67.2–89.8%) observed in the 18–25-year-old age group and the lowest prevalence of 46.3% (95% CI: 35.8–57.1%) in the 46–60-year-old age group. HR-HPV infection was found to decrease with increasing age (p < 0.001) in the overall population and according to HIV status. In contrast, LR-HPV infection was found to significantly decrease with age among HIV-negative women (p = 0.001) but not for the overall population and HIV-positive women. A proportion of 12.9% were infected with one or more HPV types covered by the Cervarix^® HPV vaccine (HPV-16 and/or -18), 18.8% (by those covered by Gardasil^®4 (HPV-6, -11, -16 and/or -18), and 42.2% by those covered by Gardasil^®9 (HPV-6, -11, -16, -18, -31, -33, -45, -52 and/or -58). The alpha-9 HPV species was the most dominant species (40.6%), followed by the alpha-7 species (29.8%). High overall HPV, HR-HPV, and alpha-9 species prevalence were observed among the women attending the public health facility. These findings contribute to the limited HPV distribution data among the Eastern Cape women, which could be used to improve HPV-related policy and assess the effectiveness of the HPV vaccination. Full article

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

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13 pages, 3219 KiB

Open AccessArticle

Soybean Bradyrhizobium spp. Spontaneously Produce Abundant and Diverse Temperate Phages in Culture

by Vanessa A. Richards, Barbra D. Ferrell, Shawn W. Polson, K. Eric Wommack and Jeffry J. Fuhrmann

Viruses 2024, 16(11), 1750; https://doi.org/10.3390/v16111750 (registering DOI) - 7 Nov 2024

Abstract

Soybean bradyrhizobia (Bradyrhizobium spp.) are symbiotic root-nodulating bacteria that fix atmospheric nitrogen for the host plant. The University of Delaware Bradyrhizobium Culture Collection (UDBCC; 353 accessions) was created to study the diversity and ecology of soybean bradyrhizobia. Some UDBCC accessions produce temperate [...] Read more.

Soybean bradyrhizobia (Bradyrhizobium spp.) are symbiotic root-nodulating bacteria that fix atmospheric nitrogen for the host plant. The University of Delaware Bradyrhizobium Culture Collection (UDBCC; 353 accessions) was created to study the diversity and ecology of soybean bradyrhizobia. Some UDBCC accessions produce temperate (lysogenic) bacteriophages spontaneously under routine culture conditions without chemical or other apparent inducing agents. Spontaneous phage production may promote horizontal gene transfer and shape bacterial genomes and associated phenotypes. A diverse subset (n = 98) of the UDBCC was examined for spontaneously produced virus-like particles (VLPs) using epifluorescent microscopy, with a majority (69%) producing detectable VLPs (>1 × 10⁷ mL⁻¹) in laboratory culture. Phages from the higher-producing accessions (>2.0 × 10⁸ VLP mL⁻¹; n = 44) were examined using transmission electron microscopy. Diverse morphologies were observed, including various tail types and lengths, capsid sizes and shapes, and the presence of collars or baseplates. In many instances, putative extracellular vesicles of a size similar to virions were also observed. Three of the four species examined (B. japonicum, B. elkanii, and B. diazoefficiens) produced apparently tailless phages. All species except B. ottawaense also produced siphovirus-like phages, while all but B. diazoefficiens additionally produced podovirus-like phages. Myovirus-like phages were restricted to B. japonicum and B. elkanii. At least three strains were polylysogens, producing up to three distinct morphotypes. These observations suggest spontaneously produced phages may play a significant role in the ecology and evolution of soybean bradyrhizobia. Full article

(This article belongs to the Section Bacterial Viruses)

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15 pages, 296 KiB

Open AccessArticle

Burden of Respiratory Syncytial Virus Infection in Children and Older Patients Hospitalized with Asthma: A Seven-Year Longitudinal Population-Based Study in Spain

by Rosa María Gomez-Garcia, Rodrigo Jiménez-Garcia, Ana López-de-Andrés, Valentín Hernández-Barrera, David Carabantes-Alarcon, José J. Zamorano-León, Natividad Cuadrado-Corrales, Ana Jiménez-Sierra and Javier De-Miguel-Diez

Viruses 2024, 16(11), 1749; https://doi.org/10.3390/v16111749 - 7 Nov 2024

Abstract

(1) Background: To describe hospitalizations due to respiratory syncytial virus (RSV) infection among children and elderly patients with asthma. (2) Methods: We used a nationwide discharge database to select patients with asthma aged 0 to 15 years and ≥65 years admitted to Spanish [...] Read more.

(1) Background: To describe hospitalizations due to respiratory syncytial virus (RSV) infection among children and elderly patients with asthma. (2) Methods: We used a nationwide discharge database to select patients with asthma aged 0 to 15 years and ≥65 years admitted to Spanish hospitals from 2016 to 2022. (3) Results: We identified 49,086 children and 471,947 elderly patients hospitalized with asthma (3.52% and 0.51%, respectively, with RSV). The proportion of RSV increased over time in children with asthma (from 1.44% to 7.4%, p < 0.001) and in elderly individuals (from 0.17% to 1.01%, p < 0.001). Among children with RSV infection, the presence of influenza (OR 3.65; 95% CI 1.46–9.1) and pneumonia (OR 1.85; 95% CI 1.02–3.55) increased the risk of poor outcome. The presence of RSV was associated with severity in these patients, defined by use of mechanical ventilation and/or admission to the intensive care unit (OR 1.44; 95% CI 1.11–1.86). In elderly patients with RSV infection, older age, congestive heart failure, COVID-19, and pneumonia increased the risk of in-hospital mortality (IHM). However, RSV infection was not associated with IHM (OR 0.88; 95% CI 0.68–1.15) in these patients. (4) Conclusion: Our results highlight the impact of RSV infection in children and elderly patients hospitalized with asthma. Strategies to improve surveillance, prophylaxis, and management of RSV infection should be evaluated. Full article

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

16 pages, 1907 KiB

Open AccessArticle

Characterizing Host microRNA: Virus Interactions of Orthoavulavirus javaense

by Megan C. Mears and Abhijeet Bakre

Viruses 2024, 16(11), 1748; https://doi.org/10.3390/v16111748 - 7 Nov 2024

Abstract

Post-transcriptional gene regulation mediated by microRNAs (miRNAs) relies on sequence complementarity between the miRNA seed site and the target gene transcript(s). This complementarity can completely inhibit or reduce translation into protein. We hypothesized that viruses employ sequence complementarity/similarity with host miRNAs to inhibit [...] Read more.

Post-transcriptional gene regulation mediated by microRNAs (miRNAs) relies on sequence complementarity between the miRNA seed site and the target gene transcript(s). This complementarity can completely inhibit or reduce translation into protein. We hypothesized that viruses employ sequence complementarity/similarity with host miRNAs to inhibit or increase the miRNA-mediated regulation of host gene expression specifically during viral infection(s). In this study, we focus on Orthoavulavirus javaense (OAVJ), the causative of Newcastle disease, a poultry disease with significant economic impact. A computational analysis of OAVJ genomes from low-virulence (lentogenic) versus virulent (velogenic) viruses was carried out to identify viral signature motifs that potentially either mimic or complement host miRNA seed sequences. Data show that OAVJ genomes harbor viral seed mimics (vSMs) or viral seed sponges (vSSs) and can mimic host miRNAs or inhibit their regulation of host genes, disrupting cellular pathways. Our analyses showed that velogens encode a statistically significant higher number of vSMs and a lower number of vSSs relative to lentogens. The number of vSMs or vSSs did not correlate with gene length. The analysis of the secondary structures flanking these vSMs and vSSs showed structural features common to miRNA precursors. The inhibition or upregulation of vSS-miR-27b-5p altered P gene expression in a sequence-dependent manner. These data demonstrate that viral transcripts can interact with host miRNAs to alter the outcomes of infection. Full article

(This article belongs to the Special Issue Viruses, MicroRNAs and Host Interactions)

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15 pages, 7750 KiB

Open AccessArticle

Longitudinal Analysis of Binding Antibody Levels Against 39 Human Adenovirus Types in Sera from 60 Regular Blood Donors from Greifswald, Germany, over 5 Years from 2018 to 2022

by Xiaoyan Wang, Konstanze Aurich, Wenli Zhang, Anja Ehrhardt, Andreas Greinacher and Wibke Bayer

Viruses 2024, 16(11), 1747; https://doi.org/10.3390/v16111747 - 7 Nov 2024

Abstract

Adenoviruses are important human pathogens that are widespread and mainly associated with respiratory and gastrointestinal infections. In a previous study on human adenovirus (HAdV) seroprevalence, we observed reduced binding antibody levels against a range of HAdV types in sera collected from students in [...] Read more.

Adenoviruses are important human pathogens that are widespread and mainly associated with respiratory and gastrointestinal infections. In a previous study on human adenovirus (HAdV) seroprevalence, we observed reduced binding antibody levels against a range of HAdV types in sera collected from students in 2021 compared to sera collected before the SARS-CoV-2 pandemic. In this follow-up study, we wanted to verify this observation in a cohort of regular blood donors for whom serial samples were available. Therefore, HAdV-specific binding antibody levels were analyzed in sera collected over a 5-year period from 2018 to 2022 in a cohort of 60 regular donors to the blood bank of the University Hospital in Greifswald, Germany. Using ELISA-based assays, we quantified the binding antibody responses against 39 HAdV types. On the cohort level, we found largely stable antibody levels over the analyzed time period, with the highest antibody responses against HAdV-C1, -D25, -D26, -E4, -D10, -D27, -C5, -D75, -C2, and -C6. Only minor but significant reductions in comparison to the first serum samples from 2018 were detected for antibody levels in 2021 and 2022 against the low-prevalent types HAdV-A31, -D8, -D20, -D37, -D65, and -D69. On the other hand, we detected fluctuations in antibody levels on the individual level, with strong increases in antibody levels indicative of novel antigen contact. Interestingly, we frequently found simultaneous changes in antibody responses against multiple HAdV types, resulting in strong correlations of antibody responses against distinct clusters of HAdVs suggesting extensive cross-reactivity of HAdV-specific antibodies. To our knowledge, this is the first study of antibodies against a broad range of HAdV types in serum samples collected from a cohort of individuals over a prolonged period, and our data provide important insight into the long-term stability of HAdV-specific antibody levels. In this cohort of regular blood donors, we did not observe any major impact of the SARS-CoV-2 pandemic on HAdV immunity. Correlations of changes in antibody levels against different types indicate cross-reactivity of HAdV-specific antibodies that are important to consider for HAdV vector development. Our data also reveal possible candidates for future development of HAdV-based vectors. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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15 pages, 2014 KiB

Open AccessReview

Emerging Insights into Memory Natural Killer Cells and Clinical Applications

by Jonida Kokiçi, Anucha Preechanukul, Helena Arellano-Ballestero, Frances Gorou and Dimitra Peppa

Viruses 2024, 16(11), 1746; https://doi.org/10.3390/v16111746 - 7 Nov 2024

Abstract

Natural killer (NK) cells are innate lymphocytes that can rapidly mount a response to their targets by employing diverse mechanisms. Due to their functional attributes, NK cells have been implicated in anti-viral and anti-tumour immune responses. Although traditionally known to mount non-specific, rapid [...] Read more.

Natural killer (NK) cells are innate lymphocytes that can rapidly mount a response to their targets by employing diverse mechanisms. Due to their functional attributes, NK cells have been implicated in anti-viral and anti-tumour immune responses. Although traditionally known to mount non-specific, rapid immune responses, in recent years, the notion of memory NK cells with adaptive features has gained more recognition. Memory NK cells emerge in response to different stimuli, such as viral antigens and specific cytokine combinations. They form distinct populations, accompanied by transcriptional, epigenetic and metabolic reprogramming, resulting in unique phenotypic and functional attributes. Several clinical trials are testing the efficacy of memory NK cells due to their enhanced functionality, bioenergetic profile and persistence in vivo. The therapeutic potential of NK cells is being harnessed in viral infections, with wider applications in the cancer field. In this review, we summarise the current state of research on the generation of memory NK cells, along with their clinical applications in viral infection and cancer. Full article

(This article belongs to the Special Issue Natural Killer Cell in Viral Infection)

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10 pages, 1135 KiB

Open AccessReview

Cyanophage Engineering for Algal Blooms Control

by Yujing Guo, Xiaoxiao Dong, Huiying Li, Yigang Tong, Zihe Liu and Jin Jin

Viruses 2024, 16(11), 1745; https://doi.org/10.3390/v16111745 - 6 Nov 2024

Abstract

Cyanobacteria represent a prevalent category of photosynthetic autotrophs capable of generating deleterious algal blooms, commonly known as cyanobacteria harmful algal blooms (cyanoHABs). These blooms often produce cyanotoxins, which pose risks to public health and ecosystems by contaminating surface waters and drinking water sources. [...] Read more.

Cyanobacteria represent a prevalent category of photosynthetic autotrophs capable of generating deleterious algal blooms, commonly known as cyanobacteria harmful algal blooms (cyanoHABs). These blooms often produce cyanotoxins, which pose risks to public health and ecosystems by contaminating surface waters and drinking water sources. Traditional treatment methods have limited effectiveness. Therefore, there is an urgent need for a new approach to effectively manage cyanoHABs. One promising approach is the use of cyanophages, which are viruses that specifically target cyanobacteria. Cyanophages serve as an effective biological control method for reducing cyanoHABs in aquatic systems. By engineering cyanophages, it is possible to develop a highly specific control strategy that minimally impacts non-target species and their propagation in the environment. This review explores the potential application of cyanophages as a strategy for controlling cyanoHABs. It includes the identification and isolation of broad-spectrum and novel cyanophages, with a specific focus on freshwater Microcystis cyanophages, highlighting their broad spectrum and high efficiency. Additionally, recent advancements in cyanophage engineering are discussed, including genome modification, functional gene identification, and the construction of artificial cyanophages. Furthermore, the current state of application is addressed. Cyanophage is a promising control strategy for effectively managing cyanoHABs in aquatic environments. Full article

(This article belongs to the Special Issue Biotechnological Applications of Phage and Phage-Derived Proteins 2025)

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16 pages, 720 KiB

Open AccessReview

How Epstein Barr Virus Causes Lymphomas

by Ya-Fang Chiu, Khongpon Ponlachantra and Bill Sugden

Viruses 2024, 16(11), 1744; https://doi.org/10.3390/v16111744 - 6 Nov 2024

Abstract

Since Epstein–Barr Virus (EBV) was isolated 60 years ago, it has been studied clinically, epidemiologically, immunologically, and molecularly in the ensuing years. These combined studies allow a broad mechanistic understanding of how this ubiquitous human pathogen which infects more than 90% of adults [...] Read more.

Since Epstein–Barr Virus (EBV) was isolated 60 years ago, it has been studied clinically, epidemiologically, immunologically, and molecularly in the ensuing years. These combined studies allow a broad mechanistic understanding of how this ubiquitous human pathogen which infects more than 90% of adults can rarely cause multiple types of lymphomas. We survey these findings to provide a coherent description of its oncogenesis. Full article

(This article belongs to the Special Issue Understanding the Oncogenesis of Human Herpesviruses through Their Critical Comparisons)

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13 pages, 2217 KiB

Open AccessArticle

Alteration of Gene Expression After Entecavir and Pegylated Interferon Therapy in HBV-Infected Chimeric Mouse Liver

by Huarui Bao, Serami Murakami, Masataka Tsuge, Takuro Uchida, Shinsuke Uchikawa, Hatsue Fujino, Atsushi Ono, Eisuke Murakami, Tomokazu Kawaoka, Daiki Miki, Clair Nelson Hayes and Shiro Oka

Viruses 2024, 16(11), 1743; https://doi.org/10.3390/v16111743 - 6 Nov 2024

Abstract

Cross-sectional analyses using liver tissue from chronic hepatitis B patients make it difficult to exclude the influence of host immune responses. In this study, we performed next-generation sequencing using the livers of hepatitis B virus (HBV)-infected uPA/SCID mice with humanized livers before and [...] Read more.

Cross-sectional analyses using liver tissue from chronic hepatitis B patients make it difficult to exclude the influence of host immune responses. In this study, we performed next-generation sequencing using the livers of hepatitis B virus (HBV)-infected uPA/SCID mice with humanized livers before and after antiviral therapy (AVT) with entecavir and pegylated interferon, and then performed a comparative transcriptome analysis of gene expression alteration. After HBV infection, the expression of genes involved in multiple pathways was significantly altered in the HBV-infected livers. After AVT, the levels of 37 out of 89 genes downregulated by HBV infection were restored, and 54 of 157 genes upregulated by HBV infection were suppressed. Interestingly, genes associated with hypoxia and KRAS signaling were included among the 54 genes upregulated by HBV infection and downregulated by AVT. Several genes associated with cell growth or carcinogenesis via hypoxia and KRAS signaling were significantly downregulated by AVT, with a potential application for the suppression of hepato-carcinogenesis. Full article

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

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25 pages, 6627 KiB

Open AccessArticle

Vesicular Stomatitis Virus Transmission Dynamics Within Its Endemic Range in Chiapas, Mexico

by Lawrence H. Zhou, Federico Valdez, Irene Lopez Gonzalez, Willian Freysser Urbina, Ariadna Ocaña, Cristell Tapia, Armando Zambrano, Edilberto Hernandez Solis, Debra P. C. Peters, Chad E. Mire, Roberto Navarro, Luis L. Rodriguez and Kathryn A. Hanley

Viruses 2024, 16(11), 1742; https://doi.org/10.3390/v16111742 - 6 Nov 2024

Abstract

Vesicular stomatitis virus (VSV), comprising vesicular stomatitis New Jersey virus (VSNJV) and vesicular stomatitis Indiana virus (VSIV), emerges from its focus of endemic transmission in Southern Mexico to cause sporadic livestock epizootics in the Western United States. A dearth of information on the [...] Read more.

Vesicular stomatitis virus (VSV), comprising vesicular stomatitis New Jersey virus (VSNJV) and vesicular stomatitis Indiana virus (VSIV), emerges from its focus of endemic transmission in Southern Mexico to cause sporadic livestock epizootics in the Western United States. A dearth of information on the role of potential arthropod vectors in the endemic region hampers efforts to identify factors that enable endemicity and predict outbreaks. In a two-year, longitudinal study at five cattle ranches in Chiapas, Mexico, insect taxa implicated as VSV vectors (blackflies, sandflies, biting midges, and mosquitoes) were collected and screened for VSV RNA, livestock vesicular stomatitis (VS) cases were monitored, and serum samples were screened for neutralizing antibodies. VS cases were reported during the rainy (n = 20) and post-rainy (n = 2) seasons. Seroprevalence against VSNJV in adult cattle was very high (75–100% per ranch) compared with VSIV (0.6%, all ranches). All four potential vector taxa were sampled, and VSNJV RNA was detected in each of them (11% VSNJV-positive of 874 total pools), while VSIV RNA was only detected in four pools of mosquitoes. Our findings indicate that VSNJV is the dominant serotype across our sampling sites with a variety of potential insect vectors involved in its transmission throughout the year. Although no livestock cases were reported in Chiapas during the dry season, VSNJV was detected in insects during this period, suggesting that mechanisms other than transmission from livestock support VSV endemicity. Full article

(This article belongs to the Section Animal Viruses)

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22 pages, 16597 KiB

Open AccessArticle

Biological Characterization and Evaluation of the Therapeutic Value of Vibrio Phages 4141 and MJW Isolated from Clinical and Sewage Water Samples of Kolkata

by Sanjoy Biswas, Devendra Nath Tewari, Alok Kumar Chakrabarti and Shanta Dutta

Viruses 2024, 16(11), 1741; https://doi.org/10.3390/v16111741 - 6 Nov 2024

Abstract

The growing prevalence of antimicrobial resistance (AMR) necessitates the development of new treatment methods to combat diseases like cholera. Lytic bacteriophages are viruses that specifically target and lyse bacteria upon infection, making them a possible treatment option for multi-drug-resistant pathogens. The current study [...] Read more.

The growing prevalence of antimicrobial resistance (AMR) necessitates the development of new treatment methods to combat diseases like cholera. Lytic bacteriophages are viruses that specifically target and lyse bacteria upon infection, making them a possible treatment option for multi-drug-resistant pathogens. The current study investigated the potential role of bacteriophages isolated from clinical stool and sewage water samples in treating multi-drug-resistant Vibrio cholerae infection, finding that over 95% of the strains were susceptible. Whole-genome sequencing (WGS) analysis revealed that both Vibrio phage 4141 (4141) and Vibrio phage MJW (MJW) contain double-stranded DNA genomes consisting of 38,498 bp (43% GC) and 49,880 bp (42.5% GC) with 46 and 64 open reading frames (ORFs), respectively. Transmission electron microscope (TEM) and WGS analysis of Vibrio phage 4141 and Vibrio phage MJW validated that they are classified under the family Autographiviridae and Zobellviridae, respectively. Furthermore, both the phages showed highly significant biofilm degradation properties. The characterization of the phages and their strict host range, high spectrum of lytic ability, high efficiency of biofilm degradation, and close genetic similarity to the therapeutic phages indicates that these phages may be useful for therapeutic purposes for treating MDR V. cholerae infection in the future. Full article

(This article belongs to the Special Issue Bacteriophage Bioinformatics 2nd Edition)

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17 pages, 7986 KiB

Open AccessArticle

Production of Oncolytic Measles Virus in Vero Cells: Impact of Culture Medium and Multiplicity of Infection

by Dustin Eckhardt, Jana Mueller, Jonas Friedrich, Jan-P. Klee, Irakli Sardlishvili, Lars E. Walter, Stefanie Fey, Peter Czermak and Denise Salzig

Viruses 2024, 16(11), 1740; https://doi.org/10.3390/v16111740 - 6 Nov 2024

Abstract

Oncolytic measles virus (MeV) is a promising anti-cancer treatment. However, the production of high titers of infectious MeV (typically 10⁷–10⁹ TCID₅₀ per dose) is challenging because the virus is unstable under typical production conditions. The objective of this study [...] Read more.

Oncolytic measles virus (MeV) is a promising anti-cancer treatment. However, the production of high titers of infectious MeV (typically 10⁷–10⁹ TCID₅₀ per dose) is challenging because the virus is unstable under typical production conditions. The objective of this study was to investigate how the multiplicity of infection (MOI) and different media—a serum-containing medium (SCM), a serum-free medium (SFM) and two chemically defined media (CDM)—affect MeV production. We infected Vero cells at MOIs of 0.02, 0.2 or 2 TCID₅₀ cell⁻¹ and the lowest MOI resulted in the largest number of infected cells towards the end of the production period. However, this did not equate to higher maximum MeV titers, which were similar for all the MOIs. The medium had a moderate effect, generating maximum titers of 0.89–2.17 × 10⁶, 1.08–1.25 × 10⁶ and 4.58–9.90 × 10⁵ TCID₅₀ mL⁻¹ for the SCM, SFM and CDM, respectively. Infection at a low MOI often required longer process times to reach maximum yields. On the other hand, a high MOI requires a large amount of MeV stock. We would therefore recommend a mid-range MOI of 0.2 TCID₅₀ cell⁻¹ for MeV production. Our findings show that SCM, SFM and CDM are equally suitable for MeV production in terms of yield and process time. This will allow MeV production in serum-free conditions, addressing the safety risks and ethical concerns associated with the use of serum. Full article

(This article belongs to the Section General Virology)

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10 pages, 539 KiB

Open AccessReview

Acute Hepatitis C: Current Status and Future Perspectives

by Massimo Fasano, Francesco Ieva, Marianna Ciarallo, Bruno Caccianotti and Teresa Antonia Santantonio

Viruses 2024, 16(11), 1739; https://doi.org/10.3390/v16111739 - 6 Nov 2024

Abstract

The hepatitis C virus (HCV) infection continues to represent a significant public health threat and is a leading cause of liver cirrhosis, liver cancer, and liver-related mortality. The World Health Organization (WHO) has set a goal for 2030: to eliminate HCV infection as [...] Read more.

The hepatitis C virus (HCV) infection continues to represent a significant public health threat and is a leading cause of liver cirrhosis, liver cancer, and liver-related mortality. The World Health Organization (WHO) has set a goal for 2030: to eliminate HCV infection as a public health threat by reducing new HCV infections by 90% and mortality by 65%. The early phase of HCV infection represents a pivotal point in the evolution of hepatitis C. Despite a favourable course in the majority of patients, approximately 50–70% of individuals with recently acquired hepatitis C will develop a chronic infection, defined as the persistence of viremia for a period exceeding six months. The diagnosis and treatment of a recent HCV infection should facilitate engagement in multidisciplinary care, prevent the development and complications of chronic liver disease, and reduce ongoing transmission in key populations. Therefore, early treatment in the early phase of infection compared with deferring treatment until the chronic infection remains a valid approach in the era of direct antiviral agents (DAAs). This approach is supported by a cost-effectiveness analysis. The aim of this review is to synthesise the existing knowledge on the early phase of hepatitis C virus infection, with a particular focus on the current risk factors, natural history, therapeutic management, and future perspectives. Full article

(This article belongs to the Special Issue Hepatitis C Virus: From Epidemiology to Treatment)

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20 pages, 1006 KiB

Open AccessReview

TRIM Proteins: Key Regulators of Immunity to Herpesvirus Infection

by Zuberwasim Sayyad, Dhiraj Acharya and Michaela U. Gack

Viruses 2024, 16(11), 1738; https://doi.org/10.3390/v16111738 - 6 Nov 2024

Abstract

Herpesviruses are ubiquitous DNA viruses that can establish latency and cause a range of mild to life-threatening diseases in humans. Upon infection, herpesviruses trigger the activation of several host antiviral defense programs that play critical roles in curbing virus replication and dissemination. Recent [...] Read more.

Herpesviruses are ubiquitous DNA viruses that can establish latency and cause a range of mild to life-threatening diseases in humans. Upon infection, herpesviruses trigger the activation of several host antiviral defense programs that play critical roles in curbing virus replication and dissemination. Recent work from many groups has integrated our understanding of TRIM (tripartite motif) proteins, a specific group of E3 ligase enzymes, as pivotal orchestrators of mammalian antiviral immunity. In this review, we summarize recent advances in the modulation of innate immune signaling by TRIM proteins during herpesvirus infection, with a focus on the detection of herpes simplex virus type 1 (HSV-1, a prototype herpesvirus) by cGAS-STING, RIG-I-like receptors, and Toll-like receptors. We also review the latest progress in understanding the intricate relationship between herpesvirus replication and TRIM protein-regulated autophagy and apoptosis. Finally, we discuss the maneuvers used by HSV-1 and other herpesviruses to overcome TRIM protein-mediated virus restriction. Full article

(This article belongs to the Special Issue TRIM Proteins in Antiviral Immunity and Virus Pathogenesis)

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24 pages, 1400 KiB

Open AccessReview

Mpox Resurgence: A Multifaceted Analysis for Global Preparedness

by Fatouma Mohamed Abdoul-Latif, Ayoub Ainane, Houda Mohamed, Ali Merito Ali, Ibrahim Houmed Aboubaker, Pannaga Pavan Jutur and Tarik Ainane

Viruses 2024, 16(11), 1737; https://doi.org/10.3390/v16111737 - 5 Nov 2024

Abstract

This study provides an in-depth analysis of mpox, encompassing its history, characteristics, epidemiology, diagnostics, treatment options, and the ongoing evolution of the virus and its transmission dynamics. Mpox, though once successfully eradicated, has re-emerged with new modes of transmission and a broader host [...] Read more.

This study provides an in-depth analysis of mpox, encompassing its history, characteristics, epidemiology, diagnostics, treatment options, and the ongoing evolution of the virus and its transmission dynamics. Mpox, though once successfully eradicated, has re-emerged with new modes of transmission and a broader host range. Genomic analyses have revealed the virus’s adaptability, posing challenges for diagnostics and vaccine efficacy. The epidemiology has shifted from sporadic zoonotic transmission in rural Africa to a significant presence in urban areas, particularly impacting high-risk populations. Advancements in diagnostics and therapeutics offer hope, but challenges persist. This work underscores the critical need for enhanced surveillance, vaccination strategies, and continued research to bolster global health systems and preparedness for future outbreaks. Full article

(This article belongs to the Special Issue Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen)

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2 pages, 135 KiB

Open AccessCorrection

Correction: Tajima et al. Amino Acids at Positions 156 and 332 in the E Protein of the West Nile Virus Subtype Kunjin Virus Classical Strain OR393 Are Involved in Plaque Size, Growth, and Pathogenicity in Mice. Viruses 2024, 16, 1237

by Shigeru Tajima, Hideki Ebihara and Chang-Kweng Lim

Viruses 2024, 16(11), 1736; https://doi.org/10.3390/v16111736 - 5 Nov 2024

Abstract

Missing Table [...] Full article

(This article belongs to the Special Issue Progress and Applications of Reverse Genetics in Virology)

25 pages, 3560 KiB

Open AccessArticle

Dimerization of Rabies Virus Phosphoprotein and Phosphorylation of Its Nucleoprotein Enhance Their Binding Affinity

by Euripedes de Almeida Ribeiro, Jr., Cédric Leyrat, Francine C. A. Gérard and Marc Jamin

Viruses 2024, 16(11), 1735; https://doi.org/10.3390/v16111735 - 4 Nov 2024

Abstract

The dynamic interplay between a multimeric phosphoprotein (P) and polymeric nucleoprotein (N) in complex with the viral RNA is at the heart of the functioning of the RNA-synthesizing machine of negative-sense RNA viruses of the order Mononegavirales. P multimerization and N phosphorylation [...] Read more.

The dynamic interplay between a multimeric phosphoprotein (P) and polymeric nucleoprotein (N) in complex with the viral RNA is at the heart of the functioning of the RNA-synthesizing machine of negative-sense RNA viruses of the order Mononegavirales. P multimerization and N phosphorylation are often cited as key factors in regulating these interactions, but a detailed understanding of the molecular mechanisms is not yet available. Working with recombinant rabies virus (RABV) N and P proteins and using mainly surface plasmon resonance, we measured the binding interactions of full-length P dimers and of two monomeric fragments of either circular or linear N-RNA complexes, and we analyzed the equilibrium binding isotherms using different models. We found that RABV P binds with nanomolar affinity to both circular and linear N-RNA complexes and that the dimerization of P protein enhances the binding affinity by 15–30-fold as compared to the monomeric fragments, but less than expected for a bivalent ligand, in which the binding domains are connected by a flexible linker. We also showed that the phosphorylation of N at Ser389 creates high-affinity sites on the polymeric N-RNA complex that enhance the binding affinity of P by a factor of about 360. Full article

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

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12 pages, 1543 KiB

Open AccessArticle

Serum microRNA 143 and 223 Gene Expression Profiles as Potential Biomarkers in Individuals with Hepatitis and COVID-19

by Lucas Lima da Silva, Luciane Almeida Amado Leon, Otacílio da Cruz Moreira, Wagner Luis da Costa Nunes Pimentel Coelho, Vanessa Duarte da Costa, Claudia Alexandra Pontes Ivantes, Priscila Pollo-Flores, Lia Laura Lewis-Ximenez, Vanessa Salete de Paula and Livia Melo Villar

Viruses 2024, 16(11), 1734; https://doi.org/10.3390/v16111734 - 4 Nov 2024

Abstract

MicroRNAs (miRNAs) can act as biomarkers and descriptors of the association between infections and other diseases, such as hepatitis and COVID-19. This study aims to investigate the role of miRNA serum expression according to laboratory data concerning hepatitis and COVID-19. Seventy individuals recruited [...] Read more.

MicroRNAs (miRNAs) can act as biomarkers and descriptors of the association between infections and other diseases, such as hepatitis and COVID-19. This study aims to investigate the role of miRNA serum expression according to laboratory data concerning hepatitis and COVID-19. Seventy individuals recruited in Southern and Southeastern Brazil donated serum samples and were divided into four groups: (i) 20 negative subjects, (ii) 20 presenting hepatitis, (iii) 19 with COVID-19 and (iv) 11 with hepatitis and COVID-19. Three miRNAs (miR-122, miR-143 and miR-223) were evaluated using real-time PCR. Hematological and biochemical markers were also analyzed. MiR-143 and miR-223 were downregulated among the hepatitis/COVID-19 group (p < 0.05). A positive correlation was observed between miR-223 and lymphocytes. There was a negative correlation between alanine transaminase (ALT) and aspartate transaminase (AST) for miR-143 and miR-223 and gamma-glutamyl transferase (GGT), alkaline phosphatase (AP) and neutrophil/lymphocyte ratio (NLR) only for miR-223 (p < 0.05). For hepatic fibrosis (FIB-4), miR-122 and miR-143 had a greater association and miR-223 was more associated with a history of vaccination against COVID-19. MicroRNAs 143 and 223 could be useful as biomarkers for hepatitis coinfection with COVID-19. Full article

(This article belongs to the Special Issue Viral Hepatitis Coinfection)

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