Viruses-Basel最新文献

{"title":"Investigation of Polymorphisms Induced by the Solo Long Terminal Repeats (Solo-LTRs) in Porcine Endogenous Retroviruses (ERVs).","authors":"Cai Chen, Zhanyu Du, Yao Zheng, Hong Chen, Ahmed A Saleh, Naisu Yang, Mengli Wang, Phiri Azele, Xiaoyan Wang, Chengyi Song","doi":"10.3390/v16111801","DOIUrl":"10.3390/v16111801","url":null,"abstract":"<p><p>Homologous recombination events take place between the 5' and 3' long terminal repeats (LTRs) of ERVs, resulting in the generation of solo-LTR, which can cause solo-LTR-associated polymorphism across different genomes. In the current study, specific criteria were established for the filtration of solo-LTRs, resulting in an average of 5630 solo-LTRs being identified in 21 genomes. Subsequently, a protocol was developed for detecting solo-LTR polymorphisms in the pig genomes, resulting in the discovery of 927 predicted solo-LTR polymorphic sites. Following verification and filtration processes, 603 highly reliable solo-LTR polymorphic sites were retained, involving 446 solo-LTR presence sites (solo-LTR⁺) and 157 solo-LTR absence sites (solo-LTR^-) relative to the reference genome. Intersection analysis with gene/functional regions revealed that 248 solo-LTR^- sites and 23 solo-LTR⁺ sites overlapped with genes or were in the vicinity of genes or functional regions, impacting a diverse range of gene structures. Moreover, through the utilization of 156 solo-LTR polymorphic sites for population genetic analysis, it was observed that these solo-LTR loci effectively clustered various breeds together, aligning with expectations and underscoring their practical utility. This study successfully established a methodology for detecting solo-LTR polymorphic sites. By applying these methods, a total of 603 high-reliability solo-LTR polymorphic sites were pinpointed, with nearly half of them being linked to genes or functional regions.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chimeric Virus-like Particles of Physalis Mottle Virus as Carriers of M2e Peptides of Influenza a Virus.","authors":"Elena A Blokhina, Eugenia S Mardanova, Anna A Zykova, Marina A Shuklina, Liudmila A Stepanova, Liudmila M Tsybalova, Nikolai V Ravin","doi":"10.3390/v16111802","DOIUrl":"10.3390/v16111802","url":null,"abstract":"<p><p>Plant viruses and virus-like particles (VLPs) are safe for mammals and can be used as a carrier/platform for the presentation of foreign antigens in vaccine development. The aim of this study was to use the coat protein (CP) of Physalis mottle virus (PhMV) as a carrier to display the extracellular domain of the transmembrane protein M2 of influenza A virus (M2e). M2e is a highly conserved antigen, but to induce an effective immune response it must be linked to an adjuvant or carrier VLP. Four tandem copies of M2e were either fused to the N-terminus of the full-length PhMV CP or replaced the 43 N-terminal amino acids of the PhMV CP. Only the first fusion protein was successfully expressed in <i>Escherichia coli</i>, where it self-assembled into spherical VLPs of about 30 nm in size. The particles were efficiently recognized by anti-M2e antibodies, indicating that the M2e peptides were exposed on the surface. Subcutaneous immunization of mice with VLPs carrying four copies of M2e induced high levels of M2e-specific IgG antibodies in serum and protected animals from a lethal influenza A virus challenge. Therefore, PhMV particles carrying M2e peptides may become useful research tools for the development of recombinant influenza vaccines.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Predictive Role of miRNAs in Hepatitis B Vaccine Response of Metabolic Dysfunction-Associated Steatotic Liver Disease Patients.","authors":"Gamze Guney Eskiler, Oguz Karabay, Mukaddes Tozlu, Ayhan Aydin, Kaan Furkan Hamarat, Umut Alkurt, Asuman Deveci Ozkan, Yasemin Gunduz","doi":"10.3390/v16111799","DOIUrl":"10.3390/v16111799","url":null,"abstract":"<p><p>(1) Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease. Although the changes in the expression levels of microRNAs (miRNAs) in hepatitis B virus-related diseases have been evaluated, no study has evaluated the role of miRNAs in HBV vaccine response in MASLD patients. We aimed to determine the miRNA expression profile in MASLD patients according to HBV vaccine response. (2) Methods: Overall, 100 MASLD patients and 100 controls were included, and anti-HBs levels were measured after three doses of HBV vaccine administration. After collecting blood samples, 22 different miRNA expression profiles were analyzed by RT-PCR analysis, and changes in the expression levels of potential miRNAs were further verified in all study groups. (3) Results: The miR-146a expression level considerably increased in MASLD patients compared to the control group. Furthermore, miR-99a and miR-640 expression levels significantly increased in AntiHBs (-) healthy individuals. (4): Conclusions: miR-146a could be used as the diagnostic marker in MASLD patients. Furthermore, the miR-99a and miR-640 expression levels could predict hepatitis B vaccine response. However, validation studies are required to verify the biomarker potential of miRNAs within a more significant number of patients.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Transcriptomics of Human Tonsils Reveals Nicotine Enhances HIV-1-Induced NLRP3 Inflammasome and Mitochondrial Activation.","authors":"Nadine Schrode, Trinisia Fortune, Aislinn M Keane, Jesse F Mangold, Benjamin Tweel, Kristin G Beaumont, Talia H Swartz","doi":"10.3390/v16111797","DOIUrl":"10.3390/v16111797","url":null,"abstract":"<p><strong>Background: </strong>HIV-1 infection, even with effective antiretroviral therapy (ART), is associated with chronic inflammation and immune dysfunction, contributing to long-term health complications. Nicotine use, prevalent among people with HIV (PWH), is known to exacerbate immune activation and disease progression, but the precise biological mechanisms remain to be fully understood. This study sought to uncover the synergistic effects of HIV-1 infection and nicotine on immune cell function, focusing on beneficial insights into NLRP3 inflammasome activation, oxidative stress, and mitochondrial pathways.</p><p><strong>Methods: </strong>Human tonsil explants were infected with HIV-1 and exposed to nicotine. Single-cell RNA sequencing was used to profile immune cell populations and gene expression linked to inflammasome activation, oxidative stress, and mitochondrial function. Gene set enrichment analysis (GSEA) and synergy assessments were conducted to investigate how nicotine modulates immune responses in the context of HIV.</p><p><strong>Results: </strong>The combination of HIV infection and nicotine exposure significantly increased NLRP3 inflammasome activation, thioredoxin, and components of oxidative phosphorylation.</p><p><strong>Conclusions: </strong>This study highlights how the combined effects of HIV-1 and nicotine offer valuable insights into immune modulation, opening doors for future therapeutic strategies. Targeting the NLRP3 inflammasome and addressing nicotine use may contribute to improved outcomes for PWH.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phylogenomic Signatures of a Lineage of Vesicular Stomatitis Indiana Virus Circulating During the 2019-2020 Epidemic in the United States.","authors":"Selene Zarate, Miranda Bertram, Case Rodgers, Kirsten Reed, Angela Pelzel-McCluskey, Ninnet Gomez-Romero, Luis L Rodriguez, Christie Mayo, Chad Mire, Sergei L Kosakovsky Pond, Lauro Velazquez-Salinas","doi":"10.3390/v16111803","DOIUrl":"10.3390/v16111803","url":null,"abstract":"<p><p>For the first time, we describe phylogenomic signatures of an epidemic lineage of vesicular stomatitis Indiana virus (VSIV). We applied multiple evolutionary analyses to a dataset of 87 full-length genome sequences representing the circulation of an epidemic VSIV lineage in the US between 2019 and 2020. Based on phylogenetic analyses, we predicted the ancestral relationship of this lineage with a specific group of isolates circulating in the endemic zone of Chiapas, Mexico. Subsequently, our findings indicate that the lineage diversified into at least four different subpopulations during its circulation in the US. We identified single nucleotide polymorphisms (SNPs) that differentiate viral subpopulations and assessed their potential relevance using comparative phylogenetic methods, highlighting the preponderance of synonymous mutations during the differentiation of these populations. Purifying selection was the main evolutionary force favoring the conservation of this epidemic phenotype, with P and G genes as the main drivers of the evolution of this lineage. Our analyses identified multiple codon sites under positive selection and the association of these sites with specific functional domains at P, M, G, and L proteins. Based on ancestral reconstruction analyses, we showed the potential relevance of some of the sites identified under positive selection to the adaptation of the epidemic lineage at the population level. Finally, using a representative group of viruses from Colorado, we established a positive correlation between genetic and geographical distances, suggesting that positive selection on specific codon positions might have favored the adaptation of different subpopulations to circulation in specific geographical settings. Collectively, our study reveals the complex dynamics that accompany the evolution of an epidemic lineage of VSIV in nature. Our analytical framework provides a model for conducting future evolutionary analyses. The ultimate goal is to support the implementation of an early warning system for vesicular stomatitis virus in the US, enabling early detection of epidemic precursors from Mexico.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Bacteriophage Pharmacokinetic Parameters After Intra-Articular Delivery in a Rat Prosthetic Joint Infection Model.","authors":"Jason Young, Mohammad Javad Shariyate, Prateek Misra, Shubham Laiwala, Ara Nazarian, Edward Kenneth Rodriguez","doi":"10.3390/v16111800","DOIUrl":"10.3390/v16111800","url":null,"abstract":"<p><p>Prosthetic joint infections (PJIs) are a serious complication of orthopedic surgery. Bacteriophage (phage) therapy shows promise as an adjunctive treatment but requires further study, particularly in its pharmacokinetics. Consequently, we performed a pharmacokinetic assessment of phage therapy for PJIs using a <i>Staphylococcus epidermidis</i> Kirschner wire-based prosthesis rat model. We used 52 male Sprague-Dawley rats in four groups: negative controls (no phage, sterile implant), PJI controls (bacteria, no phage), sterile phage (phages given, sterile implant), and PJI (bacteria, phages given). The PJI groups were inoculated with ~10⁶ CFU of <i>S. epidermidis</i>. The groups receiving phage were intra-articularly injected with ~10⁸ PFU of vB_SepM_Alex five days post-implantation. The rats were euthanized between 30 min and 48 h post-injection. The measured phage concentrations between the PJI rats and the sterile controls in periarticular tissues were not significantly different. In a noncompartmental pharmacokinetic analysis, the estimated phage half-lives were under 6 h (combined: 3.73 [IQR, 1.45, 10.07]). The maximum phage concentrations were reached within 2 h after administration (combined: 0.75 [0.50, 1.75]). The estimated phage mean residence time was approximately three hours (combined: 3.04 [1.44, 4.19]). Our study provides a preliminary set of pharmacokinetic parameters that can inform future phage dosing studies and animal models of phage therapy for PJIs.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Role of TMPRSS2 in the Proteolytic Activation of Pandemic and Zoonotic Influenza Viruses and Coronaviruses in Human Airway Cells.","authors":"Marie Schwerdtner, Luna C Schmacke, Julia Nave, Hannah Limburg, Torsten Steinmetzer, David A Stein, Hong M Moulton, Eva Böttcher-Friebertshäuser","doi":"10.3390/v16111798","DOIUrl":"10.3390/v16111798","url":null,"abstract":"<p><p>The zoonotic transmission of influenza A viruses (IAVs) and coronaviruses (CoVs) may result in severe disease. Cleavage of the surface glycoproteins hemagglutinin (HA) and spike protein (S), respectively, is essential for viral infectivity. The transmembrane serine protease 2 (TMPRSS2) is crucial for cleaving IAV HAs containing monobasic cleavage sites and severe acute respiratory syndrome (SARS)-CoV-2 S in human airway cells. Here, we analysed and compared the TMPRSS2-dependency of SARS-CoV, Middle East respiratory syndrome (MERS)-CoV, the 1918 pandemic H1N1 IAV and IAV H12, H13 and H17 subtypes in human airway cells. We used the peptide-conjugated morpholino oligomer (PPMO) T-ex5 to knockdown the expression of active TMPRSS2 and determine the impact on virus activation and replication in Calu-3 cells. The activation of H1N1/1918 and H13 relied on TMPRSS2, whereas recombinant IAVs carrying H12 or H17 were not affected by TMPRSS2 knockdown. MERS-CoV replication was strongly suppressed in T-ex5 treated cells, while SARS-CoV was less dependent on TMPRSS2. Our data underline the importance of TMPRSS2 for certain (potentially) pandemic respiratory viruses, including H1N1/1918 and MERS-CoV, in human airways, further suggesting a promising drug target. However, our findings also highlight that IAVs and CoVs differ in TMPRSS2 dependency and that other proteases are involved in virus activation.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elimination of HCV Infection: Recent Epidemiological Findings, Barriers, and Strategies for the Coming Years.","authors":"Pietro Torre, Mariano Festa, Tommaso Sarcina, Mario Masarone, Marcello Persico","doi":"10.3390/v16111792","DOIUrl":"10.3390/v16111792","url":null,"abstract":"<p><p>Hepatitis C is a disease for which in approximately 30 years we have gone from the discovery of the causative agent in 1989, to the introduction of direct-acting antiviral (DAAs) therapies starting from 2011, and to a proposal for its elimination in 2016, with some countries being on track for this goal. Elimination efforts, in the absence of a vaccine, rely on prevention measures and antiviral therapies. However, treatment rates have declined in recent years and are not considered adequate to achieve this goal at a global level. This poses a great epidemiological challenge, as HCV in many countries still causes a significant burden and most infected people are not yet diagnosed. Consequently, efforts are needed at different levels with common purposes: to facilitate access to screening and diagnosis and to improve linkage to care pathways. In this review, we discuss the latest epidemiological findings on HCV infection, the obstacles to its elimination, and strategies that are believed to be useful to overcome these obstacles but are applied unevenly across the world.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Development of Small Rodent Animal Models for Infectious Disease Research Through Vectorized Receptor Molecule Expression.","authors":"Melanie M Goens, Erin L Howard, Bryce M Warner, Leonardo Susta, Sarah K Wootton","doi":"10.3390/v16111794","DOIUrl":"10.3390/v16111794","url":null,"abstract":"<p><p>The emergence and re-emergence of pathogens with pandemic potential has been a persistent issue throughout history. Recent decades have seen significant outbreaks of zoonotic viruses from members of the <i>Coronaviridae</i>, <i>Filoviridae</i>, <i>Paramyxoviridae</i>, <i>Flaviviridae</i>, and <i>Togaviridae</i> families, resulting in widespread infections. The continual emergence of zoonotic viral pathogens and associated infections highlights the need for prevention strategies and effective treatments. Central to this effort is the availability of suitable animal models, which are essential for understanding pathogenesis and assessing transmission dynamics. These animals are also critical for evaluating the safety and efficacy of novel vaccines or therapeutics and are essential in facilitating regulatory approval of new products. Rapid development of animal models is an integral aspect of pandemic response and preparedness; however, their establishment is fraught by several rate-limiting steps, including selection of a suitable species, the logistical challenges associated with sharing and disseminating transgenic animals (e.g., the time-intensive nature of breeding and maintaining colonies), the availability of technical expertise, as well as ethical and regulatory approvals. A method for the rapid development of relevant animal models that has recently gained traction, in large part due to the COVID-19 pandemic, is the use of gene therapy vectors to express human viral receptors in readily accessible laboratory animals to enable virus infection and development of clinical disease. These models can be developed rapidly on any genetic background, making mechanistic studies and accelerated evaluation of novel countermeasures possible. In this review, we will discuss important considerations for the effective development of animal models using viral vector approaches and review the current vector-based animal models for studying viral pathogenesis and evaluating prophylactic and therapeutic strategies, with an emphasis on models of SARS-CoV-2 infection based on the vectorized expression of human angiotensin-converting enzyme 2.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding and Targeting HBV Transcription and Post-Transcriptional Regulation.","authors":"Simon P Fletcher, Rudolf K Beran","doi":"10.3390/v16111793","DOIUrl":"10.3390/v16111793","url":null,"abstract":"<p><p>Chronic hepatitis B (CHB) affects approximately 300 million people worldwide and current therapies rarely cure it [...].</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}