Viruses-Basel最新文献_第3页

APOBEC3 Proteins: From Antiviral Immunity to Oncogenic Drivers in HPV-Positive Cancers. APOBEC3蛋白：从抗病毒免疫到hpv阳性癌症的致癌驱动因素

IF 3.8 3区医学

Viruses-Basel Pub Date : 2025-03-18 DOI: 10.3390/v17030436

Eliza Pizarro Castilha, Rosalba Biondo, Kleber Paiva Trugilo, Giulia Mariane Fortunato, Timothy Robert Fenton, Karen Brajão de Oliveira

{"title":"APOBEC3 Proteins: From Antiviral Immunity to Oncogenic Drivers in HPV-Positive Cancers.","authors":"Eliza Pizarro Castilha, Rosalba Biondo, Kleber Paiva Trugilo, Giulia Mariane Fortunato, Timothy Robert Fenton, Karen Brajão de Oliveira","doi":"10.3390/v17030436","DOIUrl":"10.3390/v17030436","url":null,"abstract":"The human APOBEC superfamily consists of eleven cytidine deaminase enzymes. Among them, APOBEC3 enzymes play a dual role in antiviral immunity and cancer development. APOBEC3 enzymes, including APOBEC3A (A3A) and APOBEC3B (A3B), induce mutations in viral DNA, effectively inhibiting viral replication but also promoting somatic mutations in the host genome, contributing to cancer development. A3A and A3B are linked to mutational signatures in over 50% of human cancers, with A3A being a potent mutagen. A3B, one of the first APOBEC3 enzymes linked to carcinogenesis, plays a significant role in HPV-associated cancers by driving somatic mutagenesis and tumor progression. The A3A_B deletion polymorphism results in a hybrid A3A_B gene, leading to increased A3A expression and enhanced mutagenic potential. Such polymorphism has been linked to an elevated risk of certain cancers, particularly in populations where it is more prevalent. This review explores the molecular mechanisms of APOBEC3 proteins, highlighting their dual roles in antiviral defense and tumorigenesis. We also discuss the clinical implications of genetic variants, such as the A3A_B polymorphism, mainly in HPV infection and associated cancers, providing a comprehensive understanding of their contributions to both viral restriction and cancer development.","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721742","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}

引用次数: 0

Novel Rodent Coronavirus-like Virus Detected Among Beef Cattle with Respiratory Disease in Mexico. 在墨西哥患有呼吸道疾病的肉牛中发现了新型啮齿动物冠状病毒样病毒。

IF 3.8 3区医学

Viruses-Basel Pub Date : 2025-03-18 DOI: 10.3390/v17030433

Ismaila Shittu, Judith U Oguzie, Gustavo Hernández-Vidal, Gustavo Moreno-Degollado, Diego B Silva, Lyudmyla V Marushchak, Claudia M Trujillo-Vargas, John A Lednicky, Gregory C Gray

{"title":"Novel Rodent Coronavirus-like Virus Detected Among Beef Cattle with Respiratory Disease in Mexico.","authors":"Ismaila Shittu, Judith U Oguzie, Gustavo Hernández-Vidal, Gustavo Moreno-Degollado, Diego B Silva, Lyudmyla V Marushchak, Claudia M Trujillo-Vargas, John A Lednicky, Gregory C Gray","doi":"10.3390/v17030433","DOIUrl":"10.3390/v17030433","url":null,"abstract":"In February 2024, while conducting surveillance for novel respiratory viruses, we studied four beef cattle farms near Monterrey, Mexico. Nasal swabs were collected from sick and healthy beef cattle along with 3 h aerosol samples. None of the samples had molecular evidence of influenza A viruses. Three (8%) of thirty-six nasal swabs collected from the four farms and four (33.3%) of the twelve bioaerosol specimens had molecular evidence of influenza D virus. Five sick cow nasal swabs and one bioaerosol sample on a single farm had molecular evidence of rodent coronavirus-like (RCoV), an alphacoronavirus. Three (60%) of the five RCoV-positive cattle nasal swabs also had molecular evidence of influenza D. Attempts to isolate the RCoV in Vero-E6, LLC-MK2, MDBK, and L-2 cells were unsuccessful. However, we were able to assemble ~60% of the RCoV genome using next-generation sequencing. The six RCoV-positive samples clustered with RCoV strains identified in China in 2021. During the last 12 months, we have studied an estimated 478 dairy and beef cattle nasal swabs on 11 farms in the US and Mexico, and these RCoV detections are the first we have encountered. While feed contamination cannot be ruled out, given the propensity of CoVs to jump species and that we detected RCoV only in the noses of sick cows on this one farm, we are concerned that these findings could represent an isolated RCoV spillover event. With this report, we are alerting veterinarians and cattle farm owners of our observations that RCoV may be a new cause of bovine respiratory disease.","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722267","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}

引用次数: 0

Tegument Protein pUL47 Is Important but Not Essential for Horizontal Transmission of Vaccinal Strain SB-1 of Gallid Alphaherpesvirus 3. 被皮蛋白pUL47对鸡瘿病毒3型疫苗株SB-1的水平传播有重要作用，但不是必需的。

IF 3.8 3区医学

Viruses-Basel Pub Date : 2025-03-18 DOI: 10.3390/v17030431

Motoyuki Esaki, Mélanie Chollot, Sylvie Rémy, Katia Courvoisier-Guyader, Zoltan Penzes, David Pasdeloup, Caroline Denesvre

{"title":"Tegument Protein pUL47 Is Important but Not Essential for Horizontal Transmission of Vaccinal Strain SB-1 of Gallid Alphaherpesvirus 3.","authors":"Motoyuki Esaki, Mélanie Chollot, Sylvie Rémy, Katia Courvoisier-Guyader, Zoltan Penzes, David Pasdeloup, Caroline Denesvre","doi":"10.3390/v17030431","DOIUrl":"10.3390/v17030431","url":null,"abstract":"The gallid alphaherpesvirus 3 (GaAHV3) SB-1, a Mardivirus used as a vaccine against Marek's disease, has been proposed as an interesting viral vector for poultry vaccination. However, SB-1 is highly transmissible between chickens, a feature that may be a limitation for the use of live recombinant vaccines. We have previously shown that UL47 is essential for horizontal transmission of the pathogenic Marek's disease virus between chickens, but it is completely dispensable for replication and pathogenesis. In contrast, the role of UL47 in the biology of SB-1 remains unknown. To study that, we generated an SB-1 mutant lacking UL47 (∆47) from a commercial SB-1 isolate. This mutant replicated and spread like the WT in primary fibroblasts, indicating no growth defects in cell culture. In vivo, chickens inoculated with ∆47 had significantly reduced viral loads in the blood and the spleen, and transport to the skin was delayed compared to WT inoculated chickens. Strikingly, the ∆47 mutant was present in 66% of contact birds. As expected, 100% of contact birds were positive for the WT. In conclusion, our findings reveal that UL47 facilitates GaAHV3 SB-1 replication in vivo, which is important for latency establishment but is not essential for horizontal transmission, unlike for MDV.","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722061","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}

引用次数: 0

Risk Factors Affecting the Severity, Mortality, and Intensive Care Unit Admission of COVID-19 Patients: A Series of 1075 Cases. 1075例影响COVID-19患者严重程度、死亡率和入住重症监护病房的危险因素分析

IF 3.8 3区医学

Viruses-Basel Pub Date : 2025-03-17 DOI: 10.3390/v17030429

Ecem Narin Çopur, Dilek Ergün, Recai Ergün, Serap Atik, Hatice Türk Dağı, Muslu Kazım Körez

{"title":"Risk Factors Affecting the Severity, Mortality, and Intensive Care Unit Admission of COVID-19 Patients: A Series of 1075 Cases.","authors":"Ecem Narin Çopur, Dilek Ergün, Recai Ergün, Serap Atik, Hatice Türk Dağı, Muslu Kazım Körez","doi":"10.3390/v17030429","DOIUrl":"10.3390/v17030429","url":null,"abstract":"Background: The clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is broad; it can range from asymptomatic cases to mild upper respiratory tract illness, respiratory failure, and severe multiorgan failure resulting in death. Therefore, it is important to identify the clinical course of the disease and the factors associated with mortality.Objective: The aim of this study is to identify the risk factors associated with the severity of the disease, intensive care unit admission, and mortality in COVID-19 patients.Methods: A total of 1075 patients with clinical and radiological findings compatible with COVID-19 pneumonia and positive SARS-CoV-2 PCR were selected and retrospectively screened. All included patients were classified according to the 7th edition of the 2019 Coronavirus Disease Guidelines published by the National Health Commission of China.Results: It was observed that elevated white blood count (WBC) increased the severity of COVID-19 by 3.26 times and the risk of intensive care unit (ICU) admission by 3.47 times. Patients with high D-dimer levels had a 91% increased risk, and those with high fibrinogen levels had a 2.08 times higher risk of severe disease. High C-reactive protein (CRP) values were found to increase disease severity by 6.89 times, mortality by 12.84 times, and ICU admission by 3.37 times.Conclusions: Identifying the factors associated with disease severity, ICU admission, and mortality in COVID-19 patients could help reduce disability and mortality rates in pandemics.","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722036","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}

引用次数: 0

Exploring the Contribution of TLR7 to Sex-Based Disparities in Respiratory Syncytial Virus (RSV)-Induced Inflammation and Immunity. 探讨TLR7在呼吸道合胞病毒（RSV）诱导的炎症和免疫的性别差异中的作用。

IF 3.8 3区医学

Viruses-Basel Pub Date : 2025-03-16 DOI: 10.3390/v17030428

Mark A Miles, Thomas D Huttmann, Stella Liong, Felicia Liong, John J O'Leary, Doug A Brooks, Stavros Selemidis

{"title":"Exploring the Contribution of TLR7 to Sex-Based Disparities in Respiratory Syncytial Virus (RSV)-Induced Inflammation and Immunity.","authors":"Mark A Miles, Thomas D Huttmann, Stella Liong, Felicia Liong, John J O'Leary, Doug A Brooks, Stavros Selemidis","doi":"10.3390/v17030428","DOIUrl":"10.3390/v17030428","url":null,"abstract":"TLR7 plays a key role in recognizing viral RNA to initiate an immune response. Sex-based differences in the severity of RSV respiratory infections have been noted, and this may be related to higher expression of X-linked toll-like receptor 7 (TLR7) in female immune cells. Indeed, TLR7 has been shown to influence sex differences in responses to other respiratory viruses; however, its role in RSV infection remains underexplored. We infected adult C57Bl/6 or TLR7 knockout mice with RSV and compared the specific lung immune responses between different sexes. Gene expression analysis revealed that infected female mice had elevated levels of type I and II interferons, proinflammatory cytokines, chemokines, and viral transcripts in their lungs compared to males. Additionally, females exhibited increased numbers of macrophages and higher antibody responses in the airways. Deletion of TLR7 diminished the sex differences in certain cytokine and antibody responses. Furthermore, ex vivo infection of male alveolar macrophages with RSV resulted in greater production of proinflammatory cytokines and viral transcripts than in female macrophages, suggesting inherent sex differences in macrophage responses. These findings provide new insights into the mechanisms underlying sex differences in RSV pathophysiology and suggest that TLR7 contributes to an enhanced inflammatory response in females.","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721904","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}

引用次数: 0

Deletion of the Human Cytomegalovirus US2 to US11 Gene Family Members Impairs the Type-I Interferon Response. 人巨细胞病毒US2对US11基因家族成员的缺失会损害i型干扰素的应答

IF 3.8 3区医学

Viruses-Basel Pub Date : 2025-03-15 DOI: 10.3390/v17030426

Inessa Penner, Nadine Krämer, Julia Hirsch, Nicole Büscher, Hanno Schmidt, Bodo Plachter

{"title":"Deletion of the Human Cytomegalovirus US2 to US11 Gene Family Members Impairs the Type-I Interferon Response.","authors":"Inessa Penner, Nadine Krämer, Julia Hirsch, Nicole Büscher, Hanno Schmidt, Bodo Plachter","doi":"10.3390/v17030426","DOIUrl":"10.3390/v17030426","url":null,"abstract":"Infection of cells with the human cytomegalovirus (HCMV) triggers the expression of interferon-stimulated genes (ISGs). ISGs encode proteins with antiviral functions, such as inhibiting viral replication, promoting cell death of infected cells and enhancing immune responses. HCMV has evolved mechanisms to evade the antiviral effects of ISGs. The viral proteins encoded by the viral genes US7, US8, and US9 have been shown to interfere with interferon induction. US7 to US9 are embedded in a cluster of HCMV genes, termed US2 to US11. The individual members of this gene family interfere on multiple levels with innate and adaptive immune responses to HCMV infection. Using viral mutants with different deletions in US2 to US11, we addressed the question if genes other than US7 to US9 would also influence the IFN responses. Surprisingly, deletion of the complete US2 to US11 gene region led to reduced levels of selected ISGs. Cells infected with viruses in which individual US2 to US11 genes were deleted showed a less pronounced reduction of the selected ISGs. The experiments including RNA-seq analyses indicate that genes of the US2 to US11 gene family have a complex interaction with the IFN-ISG response which is likely regulated on the level of ISG protein stability. As US2-US11 are dispensable for replication in cell culture, the genomic region was frequently used for the insertion of bacterial artificial chromosome vectors in the process of cloning the complete HCMV genome. The results shown here must be considered when viruses derived from BACs with US2-US11 deletions are used and whether appropriate controls must be applied.","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722126","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}

引用次数: 0

Surveillance and Genomic Evolution of Infectious Precocity Virus (IPV) from 2011 to 2024. 2011 - 2024年传染性早熟病毒（IPV）监测与基因组进化

IF 3.8 3区医学

Viruses-Basel Pub Date : 2025-03-15 DOI: 10.3390/v17030425

Chengyan Zhou, Guohao Wang, Qingqing Zhou, Fanzeng Meng, Shufang Liu, Jie Huang, Xuan Dong

{"title":"Surveillance and Genomic Evolution of Infectious Precocity Virus (IPV) from 2011 to 2024.","authors":"Chengyan Zhou, Guohao Wang, Qingqing Zhou, Fanzeng Meng, Shufang Liu, Jie Huang, Xuan Dong","doi":"10.3390/v17030425","DOIUrl":"10.3390/v17030425","url":null,"abstract":"Infectious precocity virus (IPV) poses a significant economic threat to the aquaculture industry by causing sexual precocity and slow growth in Macrobrachium rosenbergii. In this study, we conducted an in-depth investigation into the genetic evolution of IPV from 2011 to 2024 by collecting 31 IPV variants through epidemiological surveys and public databases, including 29 variants with complete genomic sequences. The phylogenetic analysis revealed that these complete genomic sequences clustered into two distinct phylogenetic clades as follows: the Southeast Asian clade and the Chinese clade. Nucleotide and protein variation analyses demonstrated a high degree of similarity, with nucleotide identity ranging from 98.5% to 100% and protein identity from 99.4% to 100%. Further analysis of protein variations within the putative coding region identified two distinct variation patterns. The average dN/dS ratio of 0.12 highlights the strong purifying selection acting on IPV, particularly on structural proteins. In conclusion, this study significantly expands the genomic database of IPV and provides valuable insights into its genetic evolution. These findings offer critical scientific evidence to enhance detection protocols and support sustainable M. rosenbergii aquaculture practices.","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722135","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}

引用次数: 0

A New Approach to the Etiology of Syncope: Infection as a Cause. 晕厥病因新探：感染是病因之一。

IF 3.8 3区医学

Viruses-Basel Pub Date : 2025-03-15 DOI: 10.3390/v17030427

Branislav Milovanovic, Nikola Markovic, Masa Petrovic, Vasko Zugic, Milijana Ostojic, Milica Dragicevic-Antonic, Milovan Bojic

{"title":"A New Approach to the Etiology of Syncope: Infection as a Cause.","authors":"Branislav Milovanovic, Nikola Markovic, Masa Petrovic, Vasko Zugic, Milijana Ostojic, Milica Dragicevic-Antonic, Milovan Bojic","doi":"10.3390/v17030427","DOIUrl":"10.3390/v17030427","url":null,"abstract":"Background/objectives: Syncope is a common clinical occurrence, with neurally mediated and orthostatic types accounting for about 75% of cases. The exact pathophysiological mechanisms remain unclear, with recent evidence suggesting autonomic nervous system damage and a potential infectious etiology. This study aimed to examine the role of infection in the development of syncope and orthostatic hypotension (OH).Methods: The cross-sectional study included 806 patients from the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases \"Dedinje\". Patients were divided into three groups: unexplained recurrent syncope (n = 506), syncope with OH during the head-up tilt test (HUTT) (n = 235), and OH without a history of syncope (n = 62). All participants underwent the HUTT, and 495 underwent serological testing for various microorganisms. Data were analyzed using chi-squared tests and binary and multinomial logistic regression.Results: The HUTT was positive in 90.6% of patients with syncope and OH, compared with 61.6% with syncope alone (p < 0.001). Serological testing revealed that 57.85% of syncope patients, 62.9% of syncope with OH patients, and 78% of OH patients had positive IgM antibodies to at least one microorganism. Multivariate analysis indicated that IgM antibodies to Coxsackievirus and Epstein-Barr virus were significant predictors of OH.Conclusions: This study demonstrated a potential association between infections and syncope/OH. Further investigation into the role of infectious agents in autonomic dysfunction is warranted to clarify the underlying mechanisms of syncope and OH.","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722094","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}

引用次数: 0

A New Human SCARB2 Knock-In Mouse Model for Studying Coxsackievirus A16 and Its Neurotoxicity. 用于研究柯萨奇病毒A16及其神经毒性的新的人SCARB2敲入小鼠模型

IF 3.8 3区医学

Viruses-Basel Pub Date : 2025-03-14 DOI: 10.3390/v17030423

Haiting Wu, Ziou Wang, Yiwei Zhang, Lingfeng Hu, Jinling Yang, Caixing Zhang, Mumeng Lou, Na Pi, Qiyan Wang, Shengtao Fan, Zhangqiong Huang

{"title":"A New Human SCARB2 Knock-In Mouse Model for Studying Coxsackievirus A16 and Its Neurotoxicity.","authors":"Haiting Wu, Ziou Wang, Yiwei Zhang, Lingfeng Hu, Jinling Yang, Caixing Zhang, Mumeng Lou, Na Pi, Qiyan Wang, Shengtao Fan, Zhangqiong Huang","doi":"10.3390/v17030423","DOIUrl":"10.3390/v17030423","url":null,"abstract":"Hand, Foot, and Mouth Disease (HFMD) is a viral illness caused by enterovirus infections. While the introduction of the enterovirus 71 (EV71) vaccine has significantly reduced the number of EV71-related cases, the continued spread of Coxsackievirus A16 (CVA16) remains a major public health threat. Previous studies have shown that human SCARB2 (hSCARB2) knock-in (KI) mice, generated using embryonic stem cell (ESC) technology, are susceptible to CVA16. However, these models have failed to reproduce the clinical pathology and neurotoxicity after CVA16 infection. Therefore, there is an urgent need for a more reliable and effective animal model to study CVA16. In this study, we successfully created a hSCARB2 KI mouse model targeting the ROSA26 locus using CRISPR/Cas9 gene editing technology. The application of CRISPR/Cas9 enabled stable and widespread expression of hSCARB2 in the model. After infection, the KI mice exhibited a clinical pathology that closely mimics human infection, with prominent limb weakness and paralysis. The virus was detectable in multiple major organs of the mice, with peak viral load observed on day 7 post-infection, gradually clearing thereafter. Further analysis revealed widespread neuronal necrosis and infiltration of inflammatory cells in the brain and spinal cord of the KI mice. Additionally, significant activation of astrocytes (GFAP-positive) and microglia (IBA1-positive) was observed in the brain, suggesting that CVA16 infection may induce limb paralysis by attacking neuronal cells. Overall, this model effectively replicates the neuropathological changes induced by CVA16 infection and provides a potential experimental platform for studying CVA16-associated pathogenesis and neurotoxicity.","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722096","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}

引用次数: 0

Dual Resistance to Maribavir and Ganciclovir in Transplant Recipients. 移植受者对马里巴韦和更昔洛韦的双重耐药。

IF 3.8 3区医学

Viruses-Basel Pub Date : 2025-03-14 DOI: 10.3390/v17030421

Steven B Kleiboeker

{"title":"Dual Resistance to Maribavir and Ganciclovir in Transplant Recipients.","authors":"Steven B Kleiboeker","doi":"10.3390/v17030421","DOIUrl":"10.3390/v17030421","url":null,"abstract":"Background: Human cytomegalovirus (CMV) remains an important pathogen, especially for immunocompromised patients such as solid organ and hematopoietic stem cell recipients. Viral genomic mutations conferring drug resistance are an important impediment to effective CMV management and frequently lead to use of alternative antiviral drugs to treat CMV disease.Methods: Results from 1459 de-identified patient samples with both UL54 and UL97 sequencing results were analyzed for ganciclovir (GCV) and maribavir (MBV) resistance mutations. Genomic sequencing was performed by the Sanger method and resistance mutations were identified by comparison to CMV reference strain AD169.Results: Ganciclovir resistance was identified in 379 of 1459 (25.98%) of the samples tested, with most resistance-conferring mutations present in viral gene UL97. A total of 121 of 1459 (8.29%) samples had MBV resistance mutations, and 84 (69.42%) of the 121 samples with MBV resistance also had GCV resistance mutations. Of the 84 samples with resistance to both MBV and GCV, 35 (41.67%) had a single UL97 mutation conferring resistance to both drugs, either C480F or F342Y. The overall prevalence of C480F was increased relative to an earlier analysis of samples from this reference laboratory.Conclusions: Although a high prevalence of CMV resistance mutations was identified, this must be taken in the context of healthcare providers submitting samples from patients with suspected CMV resistance. Most MBV-resistant samples were also resistant to GCV, suggesting that use of MBV as an alternative to GCV may benefit from genotypic resistance testing to achieve the effective control of CMV disease.","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"17 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722151","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}

引用次数: 0