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Volume 16
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Viruses, Volume 16, Issue 6 (June 2024) – 93 articles

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15 pages, 3490 KiB  
Article
Exploring Dengue Dynamics: A Multi-Scale Analysis of Spatio-Temporal Trends in Ibagué, Colombia
by Julian Otero, Alejandra Tabares and Mauricio Santos-Vega
Viruses 2024, 16(6), 906; https://doi.org/10.3390/v16060906 (registering DOI) - 3 Jun 2024
Abstract
Our study examines how dengue fever incidence is associated with spatial (demographic and socioeconomic) alongside temporal (environmental) factors at multiple scales in the city of Ibagué, located in the Andean region of Colombia. We used the dengue incidence in Ibagué from 2013 to [...] Read more.
Our study examines how dengue fever incidence is associated with spatial (demographic and socioeconomic) alongside temporal (environmental) factors at multiple scales in the city of Ibagué, located in the Andean region of Colombia. We used the dengue incidence in Ibagué from 2013 to 2018 to examine the associations with climate, socioeconomic, and demographic factors from the national census and satellite imagery at four levels of local spatial aggregation. We used geographically weighted regression (GWR) to identify the relevant socioeconomic and demographic predictors, and we then integrated them with environmental variables into hierarchical models using integrated nested Laplace approximation (INLA) to analyze the spatio-temporal interactions. Our findings show a significant effect of spatial variables across the different levels of aggregation, including human population density, gas and sewage connection, percentage of woman and children, and percentage of population with a higher education degree. Lagged temporal variables displayed consistent patterns across all levels of spatial aggregation, with higher temperatures and lower precipitation at short lags showing an increase in the relative risk (RR). A comparative evaluation of the models at different levels of aggregation revealed that, while higher aggregation levels often yield a better overall model fit, finer levels offer more detailed insights into the localized impacts of socioeconomic and demographic variables on dengue incidence. Our results underscore the importance of considering macro and micro-level factors in epidemiological modeling, and they highlight the potential for targeted public health interventions based on localized risk factor analyses. Notably, the intermediate levels emerged as the most informative, thereby balancing spatial heterogeneity and case distribution density, as well as providing a robust framework for understanding the spatial determinants of dengue. Full article
(This article belongs to the Special Issue Arboviruses and Climate)
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14 pages, 2040 KiB  
Article
Lung Ultrasonography in the Evaluation of Late Sequelae of COVID-19 Pneumonia—A Comparison with Chest Computed Tomography: A Prospective Study
by Katarzyna Zimna, Małgorzata Sobiecka, Jacek Wakuliński, Dorota Wyrostkiewicz, Ewa Jankowska, Monika Szturmowicz and Witold Z. Tomkowski
Viruses 2024, 16(6), 905; https://doi.org/10.3390/v16060905 (registering DOI) - 3 Jun 2024
Abstract
The onset of the COVID-19 pandemic allowed physicians to gain experience in lung ultrasound (LUS) during the acute phase of the disease. However, limited data are available on LUS findings during the recovery phase. The aim of this study was to evaluate the [...] Read more.
The onset of the COVID-19 pandemic allowed physicians to gain experience in lung ultrasound (LUS) during the acute phase of the disease. However, limited data are available on LUS findings during the recovery phase. The aim of this study was to evaluate the utility of LUS to assess lung involvement in patients with post-COVID-19 syndrome. This study prospectively enrolled 72 patients who underwent paired LUS and chest CT scans (112 pairs including follow-up). The most frequent CT findings were ground glass opacities (83.3%), subpleural lines (72.2%), traction bronchiectasis (37.5%), and consolidations (31.9%). LUS revealed irregular pleural lines as a common abnormality initially (56.9%), along with subpleural consolidation >2.5 mm ≤10 mm (26.5%) and B-lines (26.5%). A strong correlation was found between LUS score, calculated by artificial intelligence percentage involvement in ground glass opacities described in CT (r = 0.702, p < 0.05). LUS score was significantly higher in the group with fibrotic changes compared to the non-fibrotic group with a mean value of 19.4 ± 5.7 to 11 ± 6.6, respectively (p < 0.0001). LUS might be considered valuable for examining patients with persistent symptoms after recovering from COVID-19 pneumonia. Abnormalities identified through LUS align with CT scan findings; thus, LUS might potentially reduce the need for frequent chest CT examinations. Full article
(This article belongs to the Special Issue COVID-19 and Pneumonia 3rd Edition)
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15 pages, 2007 KiB  
Review
HPV16 Phylogenetic Variants in Anogenital and Head and Neck Cancers: State of the Art and Perspectives
by Luisa Galati, Paola Di Bonito, Mariarosaria Marinaro, Maria Vincenza Chiantore and Tarik Gheit
Viruses 2024, 16(6), 904; https://doi.org/10.3390/v16060904 (registering DOI) - 3 Jun 2024
Abstract
HPV16 is responsible for approximately 60% and 90% of global HPV–induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A–D). Our understanding of HPV16 variants mostly derives from epidemiological studies [...] Read more.
HPV16 is responsible for approximately 60% and 90% of global HPV–induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A–D). Our understanding of HPV16 variants mostly derives from epidemiological studies on cervical cancer (CC) in which HPV16 B, C, and D lineages (previously named “non-European” variants) were mainly associated with high-grade cervical lesions and cancer. Although a predominance of HPV16 lineage A (previously named “European variants”) has been observed in head and neck squamous cell carcinoma (HNSCC), epidemiological and in vitro biological studies are still limited for this tumor site. Next Generation Sequencing (NGS) of the entire HPV genome has deepened our knowledge of the prevalence and distribution of HPV variants in CC and HNSCC. Research on cervical cancer has shown that certain HPV16 sublineages, such as D2, D3, A3, and A4, are associated with an increased risk of cervical cancer, and sublineages A4, D2, and D3 are linked to a higher risk of developing adenocarcinomas. Additionally, lineage C and sublineages D2 or D3 of HPV16 show an elevated risk of developing premalignant cervical lesions. However, it is still crucial to conduct large-scale studies on HPV16 variants in different HPV–related tumor sites to deeply evaluate their association with disease development and outcomes. This review discusses the current knowledge and updates on HPV16 phylogenetic variants distribution in HPV–driven anogenital and head and neck cancers. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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14 pages, 4143 KiB  
Article
HIV-1 Tat-Mediated Human Müller Glial Cell Senescence Involves Endoplasmic Reticulum Stress and Dysregulated Autophagy
by Uma Maheswari Deshetty, Nivedita Chatterjee, Shilpa Buch and Palsamy Periyasamy
Viruses 2024, 16(6), 903; https://doi.org/10.3390/v16060903 (registering DOI) - 3 Jun 2024
Abstract
Antiretroviral treatments have notably extended the lives of individuals with HIV and reduced the occurrence of comorbidities, including ocular manifestations. The involvement of endoplasmic reticulum (ER) stress in HIV-1 pathogenesis raises questions about its correlation with cellular senescence or its role in initiating [...] Read more.
Antiretroviral treatments have notably extended the lives of individuals with HIV and reduced the occurrence of comorbidities, including ocular manifestations. The involvement of endoplasmic reticulum (ER) stress in HIV-1 pathogenesis raises questions about its correlation with cellular senescence or its role in initiating senescent traits. This study investigated how ER stress and dysregulated autophagy impact cellular senescence triggered by HIV-1 Tat in the MIO-M1 cell line (human Müller glial cells). Cells exposed to HIV-1 Tat exhibited increased vimentin expression combined with markers of ER stress (BiP, p-eIF2α), autophagy (LC3, Beclin-1, p62), and the senescence marker p21 compared to control cells. Western blotting and staining techniques like SA-β-gal were employed to examine these markers. Additionally, treatments with ER stress inhibitor 4-PBA before HIV-1 Tat exposure led to a decreased expression of ER stress, senescence, and autophagy markers. Conversely, pre-treatment with the autophagy inhibitor 3-MA resulted in reduced autophagy and senescence markers but did not alter ER stress markers compared to control cells. The findings suggest a link between ER stress, dysregulated autophagy, and the initiation of a senescence phenotype in MIO-M1 cells induced by HIV-1 Tat exposure. Full article
(This article belongs to the Special Issue HIV and Drugs of Abuse, 3rd Edition)
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14 pages, 645 KiB  
Article
Factors Associated with HPV Genital Warts: A Self-Reported Cross-Sectional Study among Students and Staff of a Northern University in Nigeria
by Melvin Omone Ogbolu, Olanrewaju D. Eniade, Hussaini Majiya and Miklós Kozlovszky
Viruses 2024, 16(6), 902; https://doi.org/10.3390/v16060902 (registering DOI) - 2 Jun 2024
Abstract
The menace of human papillomavirus (HPV) infections among low- and middle-income countries with no access to a free HPV vaccine is a public health concern. HPV is one of the most common sexually transmitted infections (STIs) in Nigeria, while the most known types [...] Read more.
The menace of human papillomavirus (HPV) infections among low- and middle-income countries with no access to a free HPV vaccine is a public health concern. HPV is one of the most common sexually transmitted infections (STIs) in Nigeria, while the most known types of HPV genotypes being transmitted are the high-risk HPV-16 and 18 genotypes. In this study, we explored the predictors of self-reported HPV infections and HPV genital warts infection among a population of students, non-academic staff, and academic staff of Ibrahim Badamasi Babangida (IBB) University located in Lapai, Nigeria. We also assessed their knowledge about HPV infections and genotypes, and sexual behaviors. An online cross-sectional study was conducted by setting up a structured questionnaire on Google Forms and it was distributed to the university community via Facebook and other social media platforms of the university. The form captured questions on HPV infection, and knowledge about HPV infection and genotypes, as well as the sexual health of the participants. All variables were described using frequencies and percentage distribution; chi-squared test statistics were used to explore the association between HPV infection (medical records of HPV infection) and the participants’ profile, and a logistic regression analysis was performed to examine the factors associated with HPV genital warts infection among the population. This study reveals those participants between the ages of 26–40 years (81.3%) and those currently not in a sexually active relationship—single/divorced (26.4%)—who have self-reported having the HPV-16 and -18 genotypes. Moreover, participants between 26–40 years of age (OR: 0.45, 95%CI: 0.22–0.89) reported themselves to be carriers of HPV genital warts. Therefore, this study reveals the factors associated with HPV infection and genital warts peculiar to IBB university students and staff. Hence, we suggest the need for HPV awareness programs and free HPV vaccine availability at IBB university. Full article
(This article belongs to the Special Issue Papillomavirus-Induced Oncogenesis: Current Insights and Future Directions)
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14 pages, 2865 KiB  
Article
A Novel Strain of Fusarium oxysporum Alternavirus 1 Isolated from Fusarium oxysporum f. sp. melonis Strain T-BJ17 Confers Hypovirulence and Increases the Sensitivity of Its Host Fungus to Difenoconazole and Pydiflumetofen
by Huihui Hua, Xinyi Zhang, Li Liu and Xuehong Wu
Viruses 2024, 16(6), 901; https://doi.org/10.3390/v16060901 (registering DOI) - 2 Jun 2024
Abstract
In the current study, a novel strain of Fusarium oxysporum alternavirus 1 (FoAV1) was identified from the Fusarium oxysporum f. sp. melonis (FOM) strain T-BJ17 and was designated as Fusarium oxysporum alternavirus 1-FOM (FoAV1-FOM). Its genome consists of four dsRNA segments of 3515 [...] Read more.
In the current study, a novel strain of Fusarium oxysporum alternavirus 1 (FoAV1) was identified from the Fusarium oxysporum f. sp. melonis (FOM) strain T-BJ17 and was designated as Fusarium oxysporum alternavirus 1-FOM (FoAV1-FOM). Its genome consists of four dsRNA segments of 3515 bp (dsRNA1), 2663 bp (dsRNA2), 2368 bp (dsRNA3), and 1776 bp (dsRNA4) in length. Open reading frame 1 (ORF1) in dsRNA1 was found to encode a putative RNA-dependent RNA polymerase (RdRp), whose amino acid sequence was 99.02% identical to that of its counterpart in FoAV1; while ORF2 in dsRNA2, ORF3 in dsRNA3, and ORF4 in dsRNA4 were all found to encode hypothetical proteins. Strain T-BJ17-VF, which was verified to FoAV1-FOM-free, was obtained using single-hyphal-tip culture combined with high-temperature treatment to eliminate FoAV1-FOM from strain T-BJ17. The colony growth rate, ability to produce spores, and virulence of strain T-BJ17 were significantly lower than those of T-BJ17-VF, while the dry weight of the mycelial biomass and the sensitivity to difenoconazole and pydiflumetofen of strain T-BJ17 were greater than those of T-BJ17-VF. FoAV1-FOM was capable of 100% vertical transmission via spores. To our knowledge, this is the first time that an alternavirus has infected FOM, and this is the first report of hypovirulence and increased sensitivity to difenoconazole and pydiflumetofen induced by FoAV1-FOM infection in FOM. Full article
(This article belongs to the Collection Mycoviruses)
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21 pages, 1444 KiB  
Review
Comprehensive Overview of Broadly Neutralizing Antibodies against SARS-CoV-2 Variants
by Lingyan Cui, Tingting Li, Wenhui Xue, Sibo Zhang, Hong Wang, Hongjing Liu, Ying Gu, Ningshao Xia and Shaowei Li
Viruses 2024, 16(6), 900; https://doi.org/10.3390/v16060900 (registering DOI) - 1 Jun 2024
Abstract
Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about the possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories of broadly neutralizing [...] Read more.
Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about the possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories of broadly neutralizing antibodies (bnAbs) that retain prominent effectiveness against emerging variants including Omicron sub-lineages. The molecular characteristics, epitope conservation, and resistance mechanisms of these antibodies are further detailed, aiming to offer suggestion or direction for the development of therapeutic antibodies, and facilitate the design of vaccines with broad-spectrum potential. Full article
(This article belongs to the Special Issue SARS-CoV-2 Neutralizing Antibodies 2.0)
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24 pages, 739 KiB  
Article
Geminiviridae and Alphasatellitidae Diversity Revealed by Metagenomic Analysis of Susceptible and Tolerant Tomato Cultivars across Distinct Brazilian Biomes
by Izaías Araújo de Oliveira, Luciane de Nazaré Almeida dos Reis, Maria Esther de Noronha Fonseca, Felipe Fochat Silva Melo, Leonardo Silva Boiteux and Rita de Cássia Pereira-Carvalho
Viruses 2024, 16(6), 899; https://doi.org/10.3390/v16060899 (registering DOI) - 1 Jun 2024
Abstract
The diversity of Geminiviridae and Alphasatellitidae species in tomatoes was assessed via high-throughput sequencing of 154 symptomatic foliar samples collected from 2002 to 2017 across seven Brazilian biomes. The first pool (BP1) comprised 73 samples from the North (13), Northeast (36), and South [...] Read more.
The diversity of Geminiviridae and Alphasatellitidae species in tomatoes was assessed via high-throughput sequencing of 154 symptomatic foliar samples collected from 2002 to 2017 across seven Brazilian biomes. The first pool (BP1) comprised 73 samples from the North (13), Northeast (36), and South (24) regions. Sixteen begomoviruses and one Topilevirus were detected in BP1. Four begomovirus-like contigs were identified as putative novel species (NS). NS#1 was reported in the semi-arid (Northeast) region and NS#2 and NS#4 in mild subtropical climates (South region), whereas NS#3 was detected in the warm and humid (North) region. The second pool (BP2) comprised 81 samples from Southeast (39) and Central–West (42) regions. Fourteen viruses and subviral agents were detected in BP2, including two topileviruses, a putative novel begomovirus (NS#5), and two alphasatellites occurring in continental highland areas. The five putative novel begomoviruses displayed strict endemic distributions. Conversely, tomato mottle leaf curl virus (a monopartite species) displayed the most widespread distribution occurring across the seven sampled biomes. The overall diversity and frequency of mixed infections were higher in susceptible (16 viruses + alphasatellites) in comparison to tolerant (carrying the Ty–1 or Ty–3 introgressions) samples, which displayed 9 viruses. This complex panorama reinforces the notion that the tomato-associated Geminiviridae diversity is yet underestimated in Neotropical regions. Full article
(This article belongs to the Special Issue Diversity and Coinfections of Plant or Fungal Viruses 2023)
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22 pages, 9345 KiB  
Article
Human Coronavirus 229E Infection Inactivates Pyroptosis Executioner Gasdermin D but Ultimately Leads to Lytic Cell Death Partly Mediated by Gasdermin E
by Xavier Martiáñez-Vendrell, Jonna Bloeme-ter Horst, Roy Hutchinson, Coralie Guy, Andrew G. Bowie and Marjolein Kikkert
Viruses 2024, 16(6), 898; https://doi.org/10.3390/v16060898 (registering DOI) - 1 Jun 2024
Abstract
Human coronavirus 229E (HCoV-229E) is associated with upper respiratory tract infections and generally causes mild respiratory symptoms. HCoV-229E infection can cause cell death, but the molecular pathways that lead to virus-induced cell death as well as the interplay between viral proteins and cellular [...] Read more.
Human coronavirus 229E (HCoV-229E) is associated with upper respiratory tract infections and generally causes mild respiratory symptoms. HCoV-229E infection can cause cell death, but the molecular pathways that lead to virus-induced cell death as well as the interplay between viral proteins and cellular cell death effectors remain poorly characterized for HCoV-229E. Studying how HCoV-229E and other common cold coronaviruses interact with and affect cell death pathways may help to understand its pathogenesis and compare it to that of highly pathogenic coronaviruses. Here, we report that the main protease (Mpro) of HCoV-229E can cleave gasdermin D (GSDMD) at two different sites (Q29 and Q193) within its active N-terminal domain to generate fragments that are now unable to cause pyroptosis, a form of lytic cell death normally executed by this protein. Despite GSDMD cleavage by HCoV-229E Mpro, we show that HCoV-229E infection still leads to lytic cell death. We demonstrate that during virus infection caspase-3 cleaves and activates gasdermin E (GSDME), another key executioner of pyroptosis. Accordingly, GSDME knockout cells show a significant decrease in lytic cell death upon virus infection. Finally, we show that HCoV-229E infection leads to increased lytic cell death levels in cells expressing a GSDMD mutant uncleavable by Mpro (GSDMD Q29A+Q193A). We conclude that GSDMD is inactivated by Mpro during HCoV-229E infection, preventing GSDMD-mediated cell death, and point to the caspase-3/GSDME axis as an important player in the execution of virus-induced cell death. In the context of similar reported findings for highly pathogenic coronaviruses, our results suggest that these mechanisms do not contribute to differences in pathogenicity among coronaviruses. Nonetheless, understanding the interactions of common cold-associated coronaviruses and their proteins with the programmed cell death machineries may lead to new clues for coronavirus control strategies. Full article
(This article belongs to the Special Issue The Role of Cell Death in Viral Infections)
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7 pages, 196 KiB  
Editorial
Overview of the 2023 Physical Virology Gordon Research Conference—Viruses at Multiple Levels of Complexity
by Michael F. Hagan, Roya Zandi and Charlotte Uetrecht
Viruses 2024, 16(6), 895; https://doi.org/10.3390/v16060895 (registering DOI) - 1 Jun 2024
Abstract
This review accompanies the Special Issue on the subject of physical virology, which features work presented at the recent Gordon Research Conference (GRC) on this topic [...] Full article
(This article belongs to the Special Issue Physical Virology - Viruses at Multiple Levels of Complexity)
15 pages, 1643 KiB  
Article
Bacteriophages and Green Synthesized Zinc Oxide Nanoparticles in Combination Are Efficient against Biofilm Formation of Pseudomonas aeruginosa
by Elaheh Alipour-Khezri, Amin Moqadami, Abolfazl Barzegar, Majid Mahdavi, Mikael Skurnik and Gholamreza Zarrini
Viruses 2024, 16(6), 897; https://doi.org/10.3390/v16060897 (registering DOI) - 31 May 2024
Abstract
Bacteriophages (phages) are viruses that infect the bacteria within which their reproduction cycle takes place, a process that ends in the lysis and death of the bacterial cell. Some phages are also able to destroy bacterial biofilms. Due to increased antibiotics resistance, Pseudomonas [...] Read more.
Bacteriophages (phages) are viruses that infect the bacteria within which their reproduction cycle takes place, a process that ends in the lysis and death of the bacterial cell. Some phages are also able to destroy bacterial biofilms. Due to increased antibiotics resistance, Pseudomonas aeruginosa, another biofilm-forming pathogen, is a problem in many parts of the world. Zinc oxide (ZnO) and other metal nanoparticles (NPs) are biologically active and also possess anti-biofilm properties. ZnO-NPs were prepared by the green synthesis method using orange peels. The vibrational peaks of the ZnO-NPs were analyzed using FTIR analysis, and their size and morphological properties were determined using scanning electron microscopy (SEM). The ability of the ZnO-NPs to reduce or eliminate P. aeruginosa biofilm alone or in combination with phages PB10 and PA19 was investigated. The P. aeruginosa cells were effectively killed in the preformed 48 h biofilms during a 24 h incubation with the ZnO-NP–phage combination, in comparison with the control or ZnO-NPs alone. The treatments on growing biofilms were most efficient in the final stages of biofilm development. All five treatment groups showed a significant biofilm reduction compared to the control group (p < 0.0001) at 48 h of incubation. The influence of the ZnO-NPs and phages on the quorum sensing system of P. aeruginosa was monitored by quantitative real-time PCR (qRT-PCR) of the autoinducer biosynthesis gene lasI. While the ZnO-NPs repressed the lasI gene transcription, the phages slightly activated it at 24 and 48 h of incubation. Also, the effect of the ZnO-NPs and phage PA19 on the viability of HFF2 cells was investigated and the results showed that the combination of NPs with PA19 reduced the toxic effect of ZnO-NPs and also stimulated the growth in normal cells. Full article
(This article belongs to the Special Issue Bacteriophages and Biofilms 2.0)
18 pages, 951 KiB  
Article
Outbreaks of H5N1 High Pathogenicity Avian Influenza in South Africa in 2023 Were Caused by Two Distinct Sub-Genotypes of Clade 2.3.4.4b Viruses
by Celia Abolnik, Laura Christl Roberts, Christine Strydom, Albert Snyman and David Gordon Roberts
Viruses 2024, 16(6), 896; https://doi.org/10.3390/v16060896 (registering DOI) - 31 May 2024
Abstract
In 2023, South Africa continued to experience sporadic cases of clade 2.3.4.4b H5N1 high-pathogenicity avian influenza (HPAI) in coastal seabirds and poultry. Active environmental surveillance determined that H5Nx, H7Nx, H9Nx, H11Nx, H6N2, and H12N2, amongst other unidentified subtypes, circulated in wild birds and [...] Read more.
In 2023, South Africa continued to experience sporadic cases of clade 2.3.4.4b H5N1 high-pathogenicity avian influenza (HPAI) in coastal seabirds and poultry. Active environmental surveillance determined that H5Nx, H7Nx, H9Nx, H11Nx, H6N2, and H12N2, amongst other unidentified subtypes, circulated in wild birds and ostriches in 2023, but that H5Nx was predominant. Genome sequencing and phylogenetic analysis of confirmed H5N1 HPAI cases determined that only two of the fifteen sub-genotypes that circulated in South Africa in 2021–2022 still persisted in 2023. Sub-genotype SA13 remained restricted to coastal seabirds, with accelerated mutations observed in the neuraminidase protein. SA15 caused the chicken outbreaks, but outbreaks in the Paardeberg and George areas, in the Western Cape province, and the Camperdown region of the KwaZulu-Natal province were unrelated to each other, implicating wild birds as the source. All SA15 viruses contained a truncation in the PB1-F2 gene, but in the Western Cape SA15 chicken viruses, PA-X was putatively expressed as a novel isoform with eight additional amino acids. South African clade 2.3.4.4b H5N1 viruses had comparatively fewer markers of virulence and pathogenicity compared to European strains, a possible reason why no spillover to mammals has occurred here yet. Full article
(This article belongs to the Special Issue Virology Research in South Africa—from a Great Legacy to an Optimistic Future)
9 pages, 1667 KiB  
Article
Exploring the Epidemiological Surveillance of Hepatitis A in South Africa: A 2023 Perspective
by Keveshan Bhagwandin, Jayendrie Thaver-Kleitman, Kathleen Subramoney, Morubula Jack Manamela and Nishi Prabdial-Sing
Viruses 2024, 16(6), 894; https://doi.org/10.3390/v16060894 (registering DOI) - 31 May 2024
Abstract
Hepatitis A (HAV) presents a significant global health concern with diverse clinical manifestations primarily transmitted through fecal–oral routes, emphasizing the critical role of sanitation and water cleanliness in transmission dynamics. Age-related variations, notably asymptomatic presentation in children, add complexity. The World Health Organization’s [...] Read more.
Hepatitis A (HAV) presents a significant global health concern with diverse clinical manifestations primarily transmitted through fecal–oral routes, emphasizing the critical role of sanitation and water cleanliness in transmission dynamics. Age-related variations, notably asymptomatic presentation in children, add complexity. The World Health Organization’s (WHO) endemicity classification aids in understanding prevalence and control strategies. This study examines 2023 South African epidemiological data on HAV cases, evaluating age distribution, incidence rates, and provincial disparities. Data from the national surveillance system and weather services were analyzed. Findings reveal distinct age-related trends, with the highest seroprevalence observed in the 5–9 age group with the most burdened areas located in the Western Cape, KwaZulu-Natal, and Gauteng provinces. Furthermore, seasonal rainfall variations correlate with increased incidence in Western Cape and KZN. The amalgamation of results suggest a potential epidemiological shift, emphasizing the need for updated immunization strategies. Noteworthy patterns, like the rise in 5–9-year-olds, may be influenced by factors such as school clustering and migration. Provincial disparities and the impact of climatic events underscore the necessity for dynamic vaccination strategies and surveillance network enhancements. This study highlights the urgency for improved understanding and response to HAV in South Africa. Full article
(This article belongs to the Special Issue Virology Research in South Africa—from a Great Legacy to an Optimistic Future)
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17 pages, 5152 KiB  
Article
Co-Infection of Tobacco Rattle and Cycas Necrotic Stunt Viruses in Paeonia lactiflora: Detection Strategies, Potential Origins of Infection, and Implications for Paeonia Germplasm Conservation
by Nastassia B. Vlasava, David C. Michener, Siarhei Kharytonchyk and Liliana Cortés-Ortiz
Viruses 2024, 16(6), 893; https://doi.org/10.3390/v16060893 (registering DOI) - 31 May 2024
Abstract
Increasing reports of tobacco rattle virus (TRV) and cycas necrotic stunt virus (CNSV) in herbaceous Paeonia worldwide highlight the importance of conserving the genetic resources of this economically important ornamental and medicinal crop. The unknown origin(s) of infection, differential susceptibility of peony cultivars [...] Read more.
Increasing reports of tobacco rattle virus (TRV) and cycas necrotic stunt virus (CNSV) in herbaceous Paeonia worldwide highlight the importance of conserving the genetic resources of this economically important ornamental and medicinal crop. The unknown origin(s) of infection, differential susceptibility of peony cultivars to these viruses, and elusive disease phenotypes for CNSV in peonies make early detection and management challenging. Here, we report the presence of TRV and CNSV in plants of the University of Michigan living peony collection in the United States and a molecular characterization of their strains. Using sequences of the TRV 194 K RNA polymerase gene, we confirmed TRV infections in seven symptomatic plants (1.07% of all plants in the collection). Using newly developed primers, we recovered sequences of the CNSV RdRp gene and the polyprotein 1 gene region from nine out of twelve samples analyzed, including three from symptomless plants. Four of the nine plants had TRV and CNSV co-infections and showed more severe disease symptoms than plants only infected with TRV. Phylogenetic analyses of isolates from the University of Michigan living peony collection and publicly available isolates point to multiple origins of TRV and CNSV infections in this collection. This is the first report of TRV/CNSV co-infection and of a symptomatic detection of CNSV on cultivated P. lactiflora. Full article
(This article belongs to the Special Issue Rapid and Accurate Detection of Plant Pathogens towards Improving Biovigilance-Based Crop Management Strategies)
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29 pages, 4837 KiB  
Article
Comprehensive Identification and Characterization of HML-9 Group in Chimpanzee Genome
by Mingyue Chen, Caiqin Yang, Xiuli Zhai, Chunlei Wang, Mengying Liu, Bohan Zhang, Xing Guo, Yanglan Wang, Hanping Li, Yongjian Liu, Jingwan Han, Xiaolin Wang, Jingyun Li, Lei Jia and Lin Li
Viruses 2024, 16(6), 892; https://doi.org/10.3390/v16060892 (registering DOI) - 31 May 2024
Abstract
Endogenous retroviruses (ERVs) are related to long terminal repeat (LTR) retrotransposons, comprising gene sequences of exogenous retroviruses integrated into the host genome and inherited according to Mendelian law. They are considered to have contributed greatly to the evolution of host genome structure and [...] Read more.
Endogenous retroviruses (ERVs) are related to long terminal repeat (LTR) retrotransposons, comprising gene sequences of exogenous retroviruses integrated into the host genome and inherited according to Mendelian law. They are considered to have contributed greatly to the evolution of host genome structure and function. We previously characterized HERV-K HML-9 in the human genome. However, the biological function of this type of element in the genome of the chimpanzee, which is the closest living relative of humans, largely remains elusive. Therefore, the current study aims to characterize HML-9 in the chimpanzee genome and to compare the results with those in the human genome. Firstly, we report the distribution and genetic structural characterization of the 26 proviral elements and 38 solo LTR elements of HML-9 in the chimpanzee genome. The results showed that the distribution of these elements displayed a non-random integration pattern, and only six elements maintained a relatively complete structure. Then, we analyze their phylogeny and reveal that the identified elements all cluster together with HML-9 references and with those identified in the human genome. The HML-9 integration time was estimated based on the 2-LTR approach, and the results showed that HML-9 elements were integrated into the chimpanzee genome between 14 and 36 million years ago and into the human genome between 18 and 49 mya. In addition, conserved motifs, cis-regulatory regions, and enriched PBS sequence features in the chimpanzee genome were predicted based on bioinformatics. The results show that pathways significantly enriched for ERV LTR-regulated genes found in the chimpanzee genome are closely associated with disease development, including neurological and neurodevelopmental psychiatric disorders. In summary, the identification, characterization, and genomics of HML-9 presented here not only contribute to our understanding of the role of ERVs in primate evolution but also to our understanding of their biofunctional significance. Full article
(This article belongs to the Special Issue Retroviral Recombination and Genetic Diversity)
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8 pages, 3541 KiB  
Communication
Cytomegalovirus DNA Loads in Organs of Congenitally Infected Fetus
by Kuniaki Toriyabe, Asa Kitamura, Makoto Ikejiri, Ryotaro Hashizume, Maki Nakamura, Emi Teramoto, Hiroki Takeuchi, Eiji Kondo and Tomoaki Ikeda
Viruses 2024, 16(6), 891; https://doi.org/10.3390/v16060891 (registering DOI) - 31 May 2024
Abstract
Congenital cytomegalovirus (cCMV) infection poses significant risks to fetal development, particularly affecting the nervous system. This study reports a fetal autopsy case, examining cCMV infection and focusing on CMV DNA measurements in various fetal organs before formalin fixation, a novel approach for comprehensive [...] Read more.
Congenital cytomegalovirus (cCMV) infection poses significant risks to fetal development, particularly affecting the nervous system. This study reports a fetal autopsy case, examining cCMV infection and focusing on CMV DNA measurements in various fetal organs before formalin fixation, a novel approach for comprehensive CMV DNA evaluations in fetal organs affected by cCMV. A 20-week-old male fetus was diagnosed with cCMV following the detection of CMV DNA in ascites obtained via abdominocentesis in utero. After the termination of pregnancy, multiple organs of the fetus, including the cerebrum, thyroid gland, heart, lungs, liver, spleen, kidneys, and adrenal glands, were extracted and examined for CMV DNA loads using a real-time polymerase chain reaction. Histopathological examination involved hematoxylin–eosin and CMV-specific immunostaining. A correlation was found between CMV DNA loads and pathology, with higher CMV-infected cell numbers observed in organs positively identified with both staining methods, exhibiting CMV DNA levels of ≥1.0 × 104 copies/mL, compared to those detected solely by CMV-specific immunostaining, where CMV DNA levels ranged from 1.0 × 103 to 1.0 × 104 copies/mL. These results highlight a quantifiable relationship between the organ infection extent and CMV DNA concentration, providing insights into cCMV pathogenesis and potentially informing future diagnostic and therapeutic strategies for cCMV infection. Full article
(This article belongs to the Special Issue 65-Year Anniversary of the Discovery of Cytomegalovirus)
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20 pages, 3807 KiB  
Article
Tripartite Motif-Containing Protein 65 (TRIM65) Inhibits Hepatitis B Virus Transcription
by Sheng Shen, Ran Yan, Zhanglian Xie, Xiaoyang Yu, Hongyan Liang, Qiuhong You, Hu Zhang, Jinlin Hou, Xiaoyong Zhang, Yuanjie Liu, Jian Sun and Haitao Guo
Viruses 2024, 16(6), 890; https://doi.org/10.3390/v16060890 (registering DOI) - 31 May 2024
Abstract
Tripartite motif (TRIM) proteins, comprising a family of over 100 members with conserved motifs, exhibit diverse biological functions. Several TRIM proteins influence viral infections through direct antiviral mechanisms or by regulating host antiviral innate immune responses. To identify TRIM proteins modulating hepatitis B [...] Read more.
Tripartite motif (TRIM) proteins, comprising a family of over 100 members with conserved motifs, exhibit diverse biological functions. Several TRIM proteins influence viral infections through direct antiviral mechanisms or by regulating host antiviral innate immune responses. To identify TRIM proteins modulating hepatitis B virus (HBV) replication, we assessed 45 human TRIMs in HBV-transfected HepG2 cells. Our study revealed that ectopic expression of 12 TRIM proteins significantly reduced HBV RNA and subsequent capsid-associated DNA levels. Notably, TRIM65 uniquely downregulated viral pregenomic (pg) RNA in an HBV-promoter-specific manner, suggesting a targeted antiviral effect. Mechanistically, TRIM65 inhibited HBV replication primarily at the transcriptional level via its E3 ubiquitin ligase activity and intact B-box domain. Though HNF4α emerged as a potential TRIM65 substrate, disrupting its binding site on the HBV genome did not completely abolish TRIM65’s antiviral effect. In addition, neither HBx expression nor cellular MAVS signaling was essential to TRIM65-mediated regulation of HBV transcription. Furthermore, CRISPR-mediated knock-out of TRIM65 in the HepG2-NTCP cells boosted HBV infection, validating its endogenous role. These findings underscore TRIM proteins’ capacity to inhibit HBV transcription and highlight TRIM65’s pivotal role in this process. Full article
(This article belongs to the Special Issue HBV Transcriptional and Post-transcriptional Regulation)
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10 pages, 867 KiB  
Communication
Assessment of Survival Kinetics for Emergent Highly Pathogenic Clade 2.3.4.4 H5Nx Avian Influenza Viruses
by Caroline J. Warren, Sharon M. Brookes, Mark E. Arnold, Richard M. Irvine, Rowena D. E. Hansen, Ian H. Brown, Ashley C. Banyard and Marek J. Slomka
Viruses 2024, 16(6), 889; https://doi.org/10.3390/v16060889 (registering DOI) - 31 May 2024
Abstract
High pathogenicity avian influenza viruses (HPAIVs) cause high morbidity and mortality in poultry species. HPAIV prevalence means high numbers of infected wild birds could lead to spill over events for farmed poultry. How these pathogens survive in the environment is important for disease [...] Read more.
High pathogenicity avian influenza viruses (HPAIVs) cause high morbidity and mortality in poultry species. HPAIV prevalence means high numbers of infected wild birds could lead to spill over events for farmed poultry. How these pathogens survive in the environment is important for disease maintenance and potential dissemination. We evaluated the temperature-associated survival kinetics for five clade 2.3.4.4 H5Nx HPAIVs (UK field strains between 2014 and 2021) incubated at up to three temperatures for up to ten weeks. The selected temperatures represented northern European winter (4 °C) and summer (20 °C); and a southern European summer temperature (30 °C). For each clade 2.3.4.4 HPAIV, the time in days to reduce the viral infectivity by 90% at temperature T was established (DT), showing that a lower incubation temperature prolonged virus survival (stability), where DT ranged from days to weeks. The fastest loss of viral infectivity was observed at 30 °C. Extrapolation of the graphical DT plots to the x-axis intercept provided the corresponding time to extinction for viral decay. Statistical tests of the difference between the DT values and extinction times of each clade 2.3.4.4 strain at each temperature indicated that the majority displayed different survival kinetics from the other strains at 4 °C and 20 °C. Full article
(This article belongs to the Special Issue Evolution and Adaptation of Avian Viruses)
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17 pages, 902 KiB  
Article
Diagnosis and Characterization of Plant Viruses Using HTS to Support Virus Management and Tomato Breeding
by Enrique González-Pérez, Elizabeth Chiquito-Almanza, Salvador Villalobos-Reyes, Jaime Canul-Ku and José Luis Anaya-López
Viruses 2024, 16(6), 888; https://doi.org/10.3390/v16060888 (registering DOI) - 31 May 2024
Abstract
Viral diseases pose a significant threat to tomato crops (Solanum lycopersicum L.), one of the world’s most economically important vegetable crops. The limited genetic diversity of cultivated tomatoes contributes to their high susceptibility to viral infections. To address this challenge, tomato breeding [...] Read more.
Viral diseases pose a significant threat to tomato crops (Solanum lycopersicum L.), one of the world’s most economically important vegetable crops. The limited genetic diversity of cultivated tomatoes contributes to their high susceptibility to viral infections. To address this challenge, tomato breeding programs must harness the genetic resources found in native populations and wild relatives. Breeding efforts may aim to develop broad-spectrum resistance against the virome. To identify the viruses naturally infecting 19 advanced lines, derived from native tomatoes, high-throughput sequencing (HTS) of small RNAs and confirmation with PCR and RT-PCR were used. Single and mixed infections with tomato mosaic virus (ToMV), tomato golden mosaic virus (ToGMoV), and pepper huasteco yellow vein virus (PHYVV) were detected. The complete consensus genomes of three variants of Mexican ToMV isolates were reconstructed, potentially forming a new ToMV clade with a distinct 3’ UTR. The absence of reported mutations associated with resistance-breaking to ToMV suggests that the Tm-1, Tm-2, and Tm-22 genes could theoretically be used to confer resistance. However, the high mutation rates and a 63 nucleotide insertion in the 3’ UTR, as well as amino acid mutations in the ORFs encoding 126 KDa, 183 KDa, and MP of Mexican ToMV isolates, suggest that it is necessary to evaluate the capacity of these variants to overcome Tm-1, Tm-2, and Tm-22 resistance genes. This evaluation, along with the characterization of advanced lines using molecular markers linked to these resistant genes, will be addressed in future studies as part of the breeding strategy. This study emphasizes the importance of using HTS for accurate identification and characterization of plant viruses that naturally infect tomato germplasm based on the consensus genome sequences. This study provides crucial insights to select appropriate disease management strategies and resistance genes and guide breeding efforts toward the development of virus-resistant tomato varieties. Full article
(This article belongs to the Special Issue Diversity and Coinfections of Plant or Fungal Viruses 2023)
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12 pages, 2828 KiB  
Article
Findings and Challenges in Replacing Traditional Uterine Cervical Cancer Diagnosis with Molecular Tools in Private Gynecological Practice in Mexico
by José L. Castrillo-Diez, Carolina Rivera-Santiago, Silvia M. Ávila-Flores, Silvia A. Barrera-Barrera and Hugo A. Barrera-Saldaña
Viruses 2024, 16(6), 887; https://doi.org/10.3390/v16060887 (registering DOI) - 31 May 2024
Abstract
We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as alternatives enabled by these platforms, to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR [...] Read more.
We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as alternatives enabled by these platforms, to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR HPV)], another for the PAP test, and one more for p16/Ki67 dual-stain cytology. A total of 4499 laboratory samples were evaluated, and we found that 25.1% of low-grade samples and 47.9% of high-grade samples after PAP testing had a negative HR HPV-PCR result. In those cases, reported as Pap-negative, 22.1% had a positive HR HPV-PCR result. Dual staining with p16/Ki67 biomarkers in samples was positive for HR HPV, and 31.7% were also positive for these markers. Out of the PCR results that were positive for any of these HR HPV subtypes, n 68.3%, we did not find evidence for the presence of cancerous cells, highlighting the importance of performing dual staining with p16/Ki67 after PCR to avoid unnecessary colposcopies. The encountered challenges are a deep-rooted social reluctance in Mexico to abandon traditional Pap smears and the opinion of many specialists. Therefore, we still believe that colposcopy continues to be a preferred procedure over the dual-staining protocol. Full article
(This article belongs to the Special Issue Papillomavirus-Induced Oncogenesis: Current Insights and Future Directions)
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17 pages, 2434 KiB  
Review
The Application of Newcastle Disease Virus (NDV): Vaccine Vectors and Tumor Therapy
by Huiming Yang, Jiaxin Tian, Jing Zhao, Ye Zhao and Guozhong Zhang
Viruses 2024, 16(6), 886; https://doi.org/10.3390/v16060886 (registering DOI) - 30 May 2024
Abstract
Newcastle disease virus (NDV) is an avian pathogen with an unsegmented negative-strand RNA genome that belongs to the Paramyxoviridae family. While primarily pathogenic in birds, NDV presents no threat to human health, rendering it a safe candidate for various biomedical applications. Extensive research [...] Read more.
Newcastle disease virus (NDV) is an avian pathogen with an unsegmented negative-strand RNA genome that belongs to the Paramyxoviridae family. While primarily pathogenic in birds, NDV presents no threat to human health, rendering it a safe candidate for various biomedical applications. Extensive research has highlighted the potential of NDV as a vector for vaccine development and gene therapy, owing to its transcriptional modularity, low recombination rate, and lack of a DNA phase during replication. Furthermore, NDV exhibits oncolytic capabilities, efficiently eliciting antitumor immune responses, thereby positioning it as a promising therapeutic agent for cancer treatment. This article comprehensively reviews the biological characteristics of NDV, elucidates the molecular mechanisms underlying its oncolytic properties, and discusses its applications in the fields of vaccine vector development and tumor therapy. Full article
(This article belongs to the Special Issue Newcastle Disease and Other Avian Orthoavulaviruses 1)
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15 pages, 999 KiB  
Article
HCV Cascade of Care in HIV/HCV Co-Infected Individuals: Missed Opportunities for Micro-Elimination
by Christos Thomadakis, Dimitrios Basoulis, Olga Tsachouridou, Konstantinos Protopapas, Vasilios Paparizos, Myrto Astriti, Maria Chini, Georgios Chrysos, Markos Marangos, Periklis Panagopoulos, Diamantis Kofteridis, Helen Sambatakou, Elpida Mastrogianni, Nikos Panatzis, Evmorfia Pechlivanidou, Mina Psichοgiou and Giota Touloumi
Viruses 2024, 16(6), 885; https://doi.org/10.3390/v16060885 (registering DOI) - 30 May 2024
Abstract
People living with HIV-HCV co-infection comprise a target group for HCV-micro-elimination. We conducted an HCV cascade of care (CoC) for HIV-HCV co-infected individuals living in Greece and investigated factors associated with different HCV-CoC stages. We analyzed data from 1213 participants from the Athens [...] Read more.
People living with HIV-HCV co-infection comprise a target group for HCV-micro-elimination. We conducted an HCV cascade of care (CoC) for HIV-HCV co-infected individuals living in Greece and investigated factors associated with different HCV-CoC stages. We analyzed data from 1213 participants from the Athens Multicenter AIDS Cohort Study. A seven-stage CoC, overall and by subgroup (people who inject drugs (PWID), men having sex with men (MSM), men having sex with women (MSW), and migrants], was constructed, spanning from HCV diagnosis to sustained virologic response (SVR). Logistic/Cox regression models were employed to identify factors associated with passing through each CoC step. Among 1213 anti-HCV-positive individuals, 9.2% died before direct-acting antiviral (DAA) availability. PWID exhibited higher mortality rates than MSM. Of 1101 survivors, 72.2% remained in care and underwent HCV-RNA testing. Migrants and PWID showed the lowest retention rates. HCV-RNA was available for 79.2% of those in care, with 77.8% diagnosed with chronic HCV. Subsequently, 71% initiated DAAs, with individuals with very low CD4 counts (<100 cells/μL) exhibiting lower odds of DAA initiation. SVR testing was available for 203 individuals, with 85.7% achieving SVR. The SVR rates did not differ across risk groups. In 2023, significant gaps and between-group differences persisted in HCV-CoC among HIV-HCV co-infected individuals in Greece. Full article
(This article belongs to the Special Issue Cascade of Care for HIV and Hepatitis)
42 pages, 7808 KiB  
Article
Getting Hold of the Tobamovirus Particle—Why and How? Purification Routes over Time and a New Customizable Approach
by Tim Wendlandt, Beate Britz, Tatjana Kleinow, Katharina Hipp, Fabian J. Eber and Christina Wege
Viruses 2024, 16(6), 884; https://doi.org/10.3390/v16060884 (registering DOI) - 30 May 2024
Abstract
This article develops a multi-perspective view on motivations and methods for tobamovirus purification through the ages and presents a novel, efficient, easy-to-use approach that can be well-adapted to different species of native and functionalized virions. We survey the various driving forces prompting researchers [...] Read more.
This article develops a multi-perspective view on motivations and methods for tobamovirus purification through the ages and presents a novel, efficient, easy-to-use approach that can be well-adapted to different species of native and functionalized virions. We survey the various driving forces prompting researchers to enrich tobamoviruses, from the search for the causative agents of mosaic diseases in plants to their increasing recognition as versatile nanocarriers in biomedical and engineering applications. The best practices and rarely applied options for the serial processing steps required for successful isolation of tobamoviruses are then reviewed. Adaptations for distinct particle species, pitfalls, and ‘forgotten’ or underrepresented technologies are considered as well. The article is topped off with our own development of a method for virion preparation, rooted in historical protocols. It combines selective re-solubilization of polyethylene glycol (PEG) virion raw precipitates with density step gradient centrifugation in biocompatible iodixanol formulations, yielding ready-to-use particle suspensions. This newly established protocol and some considerations for perhaps worthwhile further developments could serve as putative stepping stones towards preparation procedures appropriate for routine practical uses of these multivalent soft-matter nanorods. Full article
(This article belongs to the Special Issue Tobamoviruses: Molecular Aspects and Resistance Regulation—a Special Issue Commemorating 125 Years of Research on Tobamoviruses)
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20 pages, 409 KiB  
Review
Molecular Markers and Mechanisms of Influenza A Virus Cross-Species Transmission and New Host Adaptation
by Xinyi Guo, Yang Zhou, Huijun Yan, Qing An, Chudan Liang, Linna Liu and Jun Qian
Viruses 2024, 16(6), 883; https://doi.org/10.3390/v16060883 (registering DOI) - 30 May 2024
Abstract
Influenza A viruses continue to be a serious health risk to people and result in a large-scale socio-economic loss. Avian influenza viruses typically do not replicate efficiently in mammals, but through the accumulation of mutations or genetic reassortment, they can overcome interspecies barriers, [...] Read more.
Influenza A viruses continue to be a serious health risk to people and result in a large-scale socio-economic loss. Avian influenza viruses typically do not replicate efficiently in mammals, but through the accumulation of mutations or genetic reassortment, they can overcome interspecies barriers, adapt to new hosts, and spread among them. Zoonotic influenza A viruses sporadically infect humans and exhibit limited human-to-human transmission. However, further adaptation of these viruses to humans may result in airborne transmissible viruses with pandemic potential. Therefore, we are beginning to understand genetic changes and mechanisms that may influence interspecific adaptation, cross-species transmission, and the pandemic potential of influenza A viruses. We also discuss the genetic and phenotypic traits associated with the airborne transmission of influenza A viruses in order to provide theoretical guidance for the surveillance of new strains with pandemic potential and the prevention of pandemics. Full article
(This article belongs to the Special Issue Animal and Human Respiratory Viruses—Causes of the Next Pandemic?)
4 pages, 186 KiB  
Editorial
Advances in Alphavirus and Flavivirus Research
by Young Chan Kim and Arturo Reyes-Sandoval
Viruses 2024, 16(6), 882; https://doi.org/10.3390/v16060882 (registering DOI) - 30 May 2024
Abstract
Newly emerging viruses, primarily zoonotic or vector-borne, pose a persistent threat to public health and have led to outbreaks of global concern [...] Full article
(This article belongs to the Special Issue Advances in Alphavirus and Flavivirus Research)
13 pages, 800 KiB  
Article
A qPCR Assay for the Quantification of Selected Genotypic Variants of Spodoptera frugiperda Multiple Nucleopolyhedrovirus (Baculoviridae)
by Cindy S. Molina-Ruiz, Jesús Alejandro Zamora-Briseño, Oihane Simón, Rodrigo Lasa and Trevor Williams
Viruses 2024, 16(6), 881; https://doi.org/10.3390/v16060881 (registering DOI) - 30 May 2024
Viewed by 49
Abstract
Alphabaculoviruses are lethal dsDNA viruses of Lepidoptera that have high genetic diversity and are transmitted in aggregates within proteinaceous occlusion bodies. This mode of transmission has implications for their efficacy as biological insecticides. A Nicaraguan isolate of Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV-NIC) comprising [...] Read more.
Alphabaculoviruses are lethal dsDNA viruses of Lepidoptera that have high genetic diversity and are transmitted in aggregates within proteinaceous occlusion bodies. This mode of transmission has implications for their efficacy as biological insecticides. A Nicaraguan isolate of Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV-NIC) comprising nine genotypic variants has been the subject of considerable study due to the influence of variant interactions on the insecticidal properties of mixed-variant occlusion bodies. As part of a systematic study on the replication and transmission of variant mixtures, a tool for the accurate quantification of a selection of genotypic variants was developed based on the quantitative PCR technique (qPCR). First, primer pairs were designed around a region of high variability in four variants named SfNic-A, SfNic-B, SfNic-C and SfNic-E to produce amplicons of 103–150 bp. Then, using cloned purified amplicons as standards, amplification was demonstrated over a dynamic range of 108–101 copies of each target. The assay was efficient (mean ± SD: 98.5 ± 0.8%), reproducible, as shown by low inter- and intra-assay coefficients of variation (<5%), and specific to the target variants (99.7–100% specificity across variants). The quantification method was validated on mixtures of genotype-specific amplicons and demonstrated accurate quantification. Finally, mixtures of the four variants were quantified based on mixtures of budded virions and mixtures of DNA extracted from occlusion-derived virions. In both cases, mixed-variant preparations compared favorably to total viral genome numbers by quantification of the polyhedrin (polh) gene that is present in all variants. This technique should prove invaluable in elucidating the influence of variant diversity on the transmission and insecticidal characteristics of this pathogen. Full article
(This article belongs to the Section Insect Viruses)
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13 pages, 1177 KiB  
Article
Rift Valley Fever Phlebovirus Reassortment Study in Sheep
by Velmurugan Balaraman, Sabarish V. Indran, In Joong Kim, Jessie D. Trujillo, David A. Meekins, Vinay Shivanna, Michelle D. Zajac, Kinga Urbaniak, Igor Morozov, Sun-Young Sunwoo, Bonto Faburay, Klaus Osterrieder, Natasha N. Gaudreault, William C. Wilson and Juergen A. Richt
Viruses 2024, 16(6), 880; https://doi.org/10.3390/v16060880 (registering DOI) - 30 May 2024
Viewed by 109
Abstract
Rift Valley fever (RVF) in ungulates and humans is caused by a mosquito-borne RVF phlebovirus (RVFV). Live attenuated vaccines are used in livestock (sheep and cattle) to control RVF in endemic regions during outbreaks. The ability of two or more different RVFV strains [...] Read more.
Rift Valley fever (RVF) in ungulates and humans is caused by a mosquito-borne RVF phlebovirus (RVFV). Live attenuated vaccines are used in livestock (sheep and cattle) to control RVF in endemic regions during outbreaks. The ability of two or more different RVFV strains to reassort when co-infecting a host cell is a significant veterinary and public health concern due to the potential emergence of newly reassorted viruses, since reassortment of RVFVs has been documented in nature and in experimental infection studies. Due to the very limited information regarding the frequency and dynamics of RVFV reassortment, we evaluated the efficiency of RVFV reassortment in sheep, a natural host for this zoonotic pathogen. Co-infection experiments were performed, first in vitro in sheep-derived cells, and subsequently in vivo in sheep. Two RVFV co-infection groups were evaluated: group I consisted of co-infection with two wild-type (WT) RVFV strains, Kenya 128B-15 (Ken06) and Saudi Arabia SA01-1322 (SA01), while group II consisted of co-infection with the live attenuated virus (LAV) vaccine strain MP-12 and a WT strain, Ken06. In the in vitro experiments, the virus supernatants were collected 24 h post-infection. In the in vivo experiments, clinical signs were monitored, and blood and tissues were collected at various time points up to nine days post-challenge for analyses. Cell culture supernatants and samples from sheep were processed, and plaque-isolated viruses were genotyped to determine reassortment frequency. Our results show that RVFV reassortment is more efficient in co-infected sheep-derived cells compared to co-infected sheep. In vitro, the reassortment frequencies reached 37.9% for the group I co-infected cells and 25.4% for the group II co-infected cells. In contrast, we detected just 1.7% reassortant viruses from group I sheep co-infected with the two WT strains, while no reassortants were detected from group II sheep co-infected with the WT and LAV strains. The results indicate that RVFV reassortment occurs at a lower frequency in vivo in sheep when compared to in vitro conditions in sheep-derived cells. Further studies are needed to better understand the implications of RVFV reassortment in relation to virulence and transmission dynamics in the host and the vector. The knowledge learned from these studies on reassortment is important for understanding the dynamics of RVFV evolution. Full article
(This article belongs to the Section Insect Viruses)
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22 pages, 5418 KiB  
Review
Mastering Death: The Roles of Viral Bcl-2 in dsDNA Viruses
by Chathura D. Suraweera, Benjamin Espinoza, Mark G. Hinds and Marc Kvansakul
Viruses 2024, 16(6), 879; https://doi.org/10.3390/v16060879 (registering DOI) - 30 May 2024
Viewed by 108
Abstract
Proteins of the Bcl-2 family regulate cellular fate via multiple mechanisms including apoptosis, autophagy, senescence, metabolism, inflammation, redox homeostasis, and calcium flux. There are several regulated cell death (RCD) pathways, including apoptosis and autophagy, that use distinct molecular mechanisms to elicit the death [...] Read more.
Proteins of the Bcl-2 family regulate cellular fate via multiple mechanisms including apoptosis, autophagy, senescence, metabolism, inflammation, redox homeostasis, and calcium flux. There are several regulated cell death (RCD) pathways, including apoptosis and autophagy, that use distinct molecular mechanisms to elicit the death response. However, the same proteins/genes may be deployed in multiple biochemical pathways. In apoptosis, Bcl-2 proteins control the integrity of the mitochondrial outer membrane (MOM) by regulating the formation of pores in the MOM and apoptotic cell death. A number of prosurvival genes populate the genomes of viruses including those of the pro-survival Bcl-2 family. Viral Bcl-2 proteins are sequence and structural homologs of their cellular counterparts and interact with cellular proteins in apoptotic and autophagic pathways, potentially allowing them to modulate these pathways and determine cellular fate. Full article
(This article belongs to the Special Issue Apoptosis and Necroptosis as Host Defense Strategies to Prevent Viral Infection)
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22 pages, 4111 KiB  
Article
Exploring Cannabinoids as Potential Inhibitors of SARS-CoV-2 Papain-like Protease: Insights from Computational Analysis and Molecular Dynamics Simulations
by Jamie Holmes, Shahidul M. Islam and Kimberly A. Milligan
Viruses 2024, 16(6), 878; https://doi.org/10.3390/v16060878 (registering DOI) - 30 May 2024
Viewed by 121
Abstract
The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global COVID-19 pandemic, challenging healthcare systems worldwide. Effective therapeutic strategies against this novel coronavirus remain limited, underscoring the urgent need for innovative approaches. The present research investigates the potential [...] Read more.
The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global COVID-19 pandemic, challenging healthcare systems worldwide. Effective therapeutic strategies against this novel coronavirus remain limited, underscoring the urgent need for innovative approaches. The present research investigates the potential of cannabis compounds as therapeutic agents against SARS-CoV-2 through their interaction with the virus’s papain-like protease (PLpro) protein, a crucial element in viral replication and immune evasion. Computational methods, including molecular docking and molecular dynamics (MD) simulations, were employed to screen cannabis compounds against PLpro and analyze their binding mechanisms and interaction patterns. The results showed cannabinoids with binding affinities ranging from −6.1 kcal/mol to −4.6 kcal/mol, forming interactions with PLpro. Notably, Cannabigerolic and Cannabidiolic acids exhibited strong binding contacts with critical residues in PLpro’s active region, indicating their potential as viral replication inhibitors. MD simulations revealed the dynamic behavior of cannabinoid–PLpro complexes, highlighting stable binding conformations and conformational changes over time. These findings shed light on the mechanisms underlying cannabis interaction with SARS-CoV-2 PLpro, aiding in the rational design of antiviral therapies. Future research will focus on experimental validation, optimizing binding affinity and selectivity, and preclinical assessments to develop effective treatments against COVID-19. Full article
(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)
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17 pages, 2766 KiB  
Article
cGAS-STING-TBK1 Signaling Promotes Valproic Acid-Responsive Human Cytomegalovirus Immediate-Early Transcription during Infection of Incompletely Differentiated Myeloid Cells
by Emily R. Albright and Robert F. Kalejta
Viruses 2024, 16(6), 877; https://doi.org/10.3390/v16060877 (registering DOI) - 30 May 2024
Viewed by 113
Abstract
Repression of human cytomegalovirus (HCMV) immediate-early (IE) gene expression is a key regulatory step in the establishment and maintenance of latent reservoirs. Viral IE transcription and protein accumulation can be elevated during latency by treatment with histone deacetylase inhibitors such as valproic acid [...] Read more.
Repression of human cytomegalovirus (HCMV) immediate-early (IE) gene expression is a key regulatory step in the establishment and maintenance of latent reservoirs. Viral IE transcription and protein accumulation can be elevated during latency by treatment with histone deacetylase inhibitors such as valproic acid (VPA), rendering infected cells visible to adaptive immune responses. However, the latency-associated viral protein UL138 inhibits the ability of VPA to enhance IE gene expression during infection of incompletely differentiated myeloid cells that support latency. UL138 also limits the accumulation of IFNβ transcripts by inhibiting the cGAS-STING-TBK1 DNA-sensing pathway. Here, we show that, in the absence of UL138, the cGAS-STING-TBK1 pathway promotes both IFNβ accumulation and VPA-responsive IE gene expression in incompletely differentiated myeloid cells. Inactivation of this pathway by either genetic or pharmacological inhibition phenocopied UL138 expression and reduced VPA-responsive IE transcript and protein accumulation. This work reveals a link between cytoplasmic pathogen sensing and epigenetic control of viral lytic phase transcription and suggests that manipulation of pattern recognition receptor signaling pathways could aid in the refinement of MIEP regulatory strategies to target latent viral reservoirs. Full article
(This article belongs to the Special Issue Epigenetic and Transcriptional Regulation of DNA Virus Infections)
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