Enteroviruses are a genus of small RNA viruses that are responsible for approximately one billion global infections annually. These infections range in severity from the common cold and flu-like symptoms to more severe diseases, such as viral myocarditis, pancreatitis, and neurological disorders, that continue to pose a global health challenge with limited therapeutic strategies currently available. In the current study, we sought to understand the interaction between coxsackievirus B3 (CVB3), which is a model enterovirus, and macrophage cells, as there is limited understanding of how this virus interacts with macrophage innate immune cells. Our study demonstrated that CVB3 can robustly activate macrophages without apparent viral replication in these cells. We also showed that myeloid cells lacked the viral entry receptor coxsackievirus and adenovirus receptor (CAR). However, the expression of exogenous CAR in RAW264.7 macrophages was unable to overcome the viral replication deficit. Interestingly, the CAR expression was associated with altered inflammatory responses during prolonged infection. Additionally, we identified the autophagy protein LC3 as a novel stimulus for macrophage activation. These findings provide new insights into the mechanisms of CVB3-induced macrophage activation and its implications for viral pathogenesis.
{"title":"Coxsackievirus B3 Activates Macrophages Independently of CAR-Mediated Viral Entry","authors":"Yasir Mohamud, Jingfei Carly Lin, Sinwoo Wendy Hwang, Amirhossein Bahreyni, Zhihan Claire Wang, Honglin Luo","doi":"10.3390/v16091456","DOIUrl":"https://doi.org/10.3390/v16091456","url":null,"abstract":"Enteroviruses are a genus of small RNA viruses that are responsible for approximately one billion global infections annually. These infections range in severity from the common cold and flu-like symptoms to more severe diseases, such as viral myocarditis, pancreatitis, and neurological disorders, that continue to pose a global health challenge with limited therapeutic strategies currently available. In the current study, we sought to understand the interaction between coxsackievirus B3 (CVB3), which is a model enterovirus, and macrophage cells, as there is limited understanding of how this virus interacts with macrophage innate immune cells. Our study demonstrated that CVB3 can robustly activate macrophages without apparent viral replication in these cells. We also showed that myeloid cells lacked the viral entry receptor coxsackievirus and adenovirus receptor (CAR). However, the expression of exogenous CAR in RAW264.7 macrophages was unable to overcome the viral replication deficit. Interestingly, the CAR expression was associated with altered inflammatory responses during prolonged infection. Additionally, we identified the autophagy protein LC3 as a novel stimulus for macrophage activation. These findings provide new insights into the mechanisms of CVB3-induced macrophage activation and its implications for viral pathogenesis.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthias Licheri, Manon Flore Licheri, Kemal Mehinagic, Emilia Radulovic, Nicolas Ruggli, Ronald Dijkman
African swine fever virus (ASFV) has been spreading through Europe, Asia, and the Caribbean after its introduction in Georgia in 2007 and, due to its particularly high mortality rate, poses a continuous threat to the pig industry. The golden standard to trace back the ASFV is whole genome sequencing, but it is a cost and time-intensive methodology. A more efficient way of tracing the virus is to amplify only specific genomic regions relevant for genotyping. This is mainly accomplished by amplifying single amplicons by PCR followed by Sanger sequencing. To reduce costs and processivity time, we evaluated a multiplex PCR based on the four primer sets routinely used for ASFV genotyping (B646L, E183L, B602L, and intergenic I73R-I329L), which was followed by Nanopore ligation-based amplicon sequencing. We show that with this protocol, we can genotype ASFV DNA originating from different biological matrices and correctly classify multiple genotypes and strains using a single PCR reaction. Further optimization of this method can be accomplished by adding or swapping the primer sets used for amplification based on the needs of a specific country or region, making it a versatile tool that can speed up the processing time and lower the costs of genotyping during ASFV outbreaks.
{"title":"Multiplex PCR Approach for Rapid African Swine Fever Virus Genotyping","authors":"Matthias Licheri, Manon Flore Licheri, Kemal Mehinagic, Emilia Radulovic, Nicolas Ruggli, Ronald Dijkman","doi":"10.3390/v16091460","DOIUrl":"https://doi.org/10.3390/v16091460","url":null,"abstract":"African swine fever virus (ASFV) has been spreading through Europe, Asia, and the Caribbean after its introduction in Georgia in 2007 and, due to its particularly high mortality rate, poses a continuous threat to the pig industry. The golden standard to trace back the ASFV is whole genome sequencing, but it is a cost and time-intensive methodology. A more efficient way of tracing the virus is to amplify only specific genomic regions relevant for genotyping. This is mainly accomplished by amplifying single amplicons by PCR followed by Sanger sequencing. To reduce costs and processivity time, we evaluated a multiplex PCR based on the four primer sets routinely used for ASFV genotyping (B646L, E183L, B602L, and intergenic I73R-I329L), which was followed by Nanopore ligation-based amplicon sequencing. We show that with this protocol, we can genotype ASFV DNA originating from different biological matrices and correctly classify multiple genotypes and strains using a single PCR reaction. Further optimization of this method can be accomplished by adding or swapping the primer sets used for amplification based on the needs of a specific country or region, making it a versatile tool that can speed up the processing time and lower the costs of genotyping during ASFV outbreaks.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cicek Topcu, Bram Vrancken, Johana Hezka Rodosthenous, David van de Vijver, Georgios Siakallis, Philippe Lemey, Leondios G. Kostrikis
The human immunodeficiency virus type 1 (HIV-1) epidemic has been a major public health threat on a global scale since the early 1980s. Despite the introduction of combination antiretroviral therapy (cART), the incidence of new HIV-1 infections continues to rise in some regions around the world. Thus, with the continuous transmission of HIV-1 and the lack of a cure, it is imperative for molecular epidemiological studies to be performed, to monitor the infection and ultimately be able to control the spread of this virus. This work provides a comprehensive molecular epidemiological analysis of the HIV-1 infection in Cyprus, through examining 305 HIV-1 sequences collected between 9 March 2017 and 14 October 2021. Employing advanced statistical and bioinformatic techniques, the research delved deeply into understanding the transmission dynamics of the HIV-1 epidemic in Cyprus, as well as the monitoring of HIV-1’s genetic diversity and the surveillance of transmitted drug resistance. The characterization of Cyprus’s HIV-1 epidemic revealed a diverse landscape, comprising 21 HIV-1 group M pure subtypes and circulating recombinant forms (CRFs), alongside numerous uncharacterized recombinant strains. Subtypes A1 and B emerged as the most prevalent strains, followed by CRF02_AG. The findings of this study also revealed high levels of transmitted drug resistance (TDR) patterns, raising concerns for the efficacy of cART. The demographic profiles of individuals involved in HIV-1 transmission underscored the disproportionate burden borne by young to middle-aged Cypriot males, particularly those in the MSM community, who reported contracting the virus in Cyprus. An assessment of the spatiotemporal evolutionary dynamics illustrated the global interconnectedness of HIV-1 transmission networks, implicating five continents in the dissemination of strains within Cyprus: Europe, Africa, Asia, North America, and Oceania. Overall, this study advances the comprehension of the HIV-1 epidemic in Cyprus and highlights the importance of understanding HIV-1’s transmission dynamics through continuous surveillance efforts. Furthermore, this work emphasizes the critical role of state-of-the-art bioinformatics analyses in addressing the challenges posed by HIV-1 transmission globally, laying the groundwork for public health interventions aimed at curbing its spread and improving patient outcomes.
{"title":"Mapping Transmission Dynamics and Drug Resistance Surveillance in the Cyprus HIV-1 Epidemic (2017–2021)","authors":"Cicek Topcu, Bram Vrancken, Johana Hezka Rodosthenous, David van de Vijver, Georgios Siakallis, Philippe Lemey, Leondios G. Kostrikis","doi":"10.3390/v16091449","DOIUrl":"https://doi.org/10.3390/v16091449","url":null,"abstract":"The human immunodeficiency virus type 1 (HIV-1) epidemic has been a major public health threat on a global scale since the early 1980s. Despite the introduction of combination antiretroviral therapy (cART), the incidence of new HIV-1 infections continues to rise in some regions around the world. Thus, with the continuous transmission of HIV-1 and the lack of a cure, it is imperative for molecular epidemiological studies to be performed, to monitor the infection and ultimately be able to control the spread of this virus. This work provides a comprehensive molecular epidemiological analysis of the HIV-1 infection in Cyprus, through examining 305 HIV-1 sequences collected between 9 March 2017 and 14 October 2021. Employing advanced statistical and bioinformatic techniques, the research delved deeply into understanding the transmission dynamics of the HIV-1 epidemic in Cyprus, as well as the monitoring of HIV-1’s genetic diversity and the surveillance of transmitted drug resistance. The characterization of Cyprus’s HIV-1 epidemic revealed a diverse landscape, comprising 21 HIV-1 group M pure subtypes and circulating recombinant forms (CRFs), alongside numerous uncharacterized recombinant strains. Subtypes A1 and B emerged as the most prevalent strains, followed by CRF02_AG. The findings of this study also revealed high levels of transmitted drug resistance (TDR) patterns, raising concerns for the efficacy of cART. The demographic profiles of individuals involved in HIV-1 transmission underscored the disproportionate burden borne by young to middle-aged Cypriot males, particularly those in the MSM community, who reported contracting the virus in Cyprus. An assessment of the spatiotemporal evolutionary dynamics illustrated the global interconnectedness of HIV-1 transmission networks, implicating five continents in the dissemination of strains within Cyprus: Europe, Africa, Asia, North America, and Oceania. Overall, this study advances the comprehension of the HIV-1 epidemic in Cyprus and highlights the importance of understanding HIV-1’s transmission dynamics through continuous surveillance efforts. Furthermore, this work emphasizes the critical role of state-of-the-art bioinformatics analyses in addressing the challenges posed by HIV-1 transmission globally, laying the groundwork for public health interventions aimed at curbing its spread and improving patient outcomes.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hainian Zhao, Zhiyun Gao, Jiawen Sun, Hongxiu Qiao, Yan Zhao, Yan Cui, Baoxin Zhao, Weijie Wang, Sandra Chiu, Xia Chuai
Enteroviruses such as coxsackievirus B3 are identified as a common cause of viral myocarditis, but the potential mechanism of its replication and pathogenesis are largely unknown. The genomes of a variety of viruses contain N6-methyladenosine (m6A), which plays important roles in virus replication. Here, by using the online bioinformatics tools SRAMP and IF, we predict that the CVB3 genome contains m6A sites and found that CVB3 infection could alter the expression and cellular localization of m6A-related proteins. Moreover, we found that 3-deazaadenosine (3-DAA), an m6A modification inhibitor, significantly decreased CVB3 replication. We also observed that the m6A methyltransferases methyltransferase-like protein 3 (METTL3) and METTL14 play positive roles in CVB3 replication, whereas m6A demethylases fat mass and obesity-associated protein (FTO) or AlkB homolog 5 (ALKBH5) have opposite effects. Knockdown of the m6A binding proteins YTH domain family protein 1 (YTHDF1), YTHDF2 and YTHDF3 strikingly decreased CVB3 replication. Finally, the m6A site mutation in the CVB3 genome decreased the replication of CVB3 compared with that in the CVB3 wild-type (WT) strain. Taken together, our results demonstrated that CVB3 could exploit m6A modification to promote viral replication, which provides new insights into the mechanism of the interaction between CVB3 and the host.
{"title":"N6-Methyladenosine Positively Regulates Coxsackievirus B3 Replication","authors":"Hainian Zhao, Zhiyun Gao, Jiawen Sun, Hongxiu Qiao, Yan Zhao, Yan Cui, Baoxin Zhao, Weijie Wang, Sandra Chiu, Xia Chuai","doi":"10.3390/v16091448","DOIUrl":"https://doi.org/10.3390/v16091448","url":null,"abstract":"Enteroviruses such as coxsackievirus B3 are identified as a common cause of viral myocarditis, but the potential mechanism of its replication and pathogenesis are largely unknown. The genomes of a variety of viruses contain N6-methyladenosine (m6A), which plays important roles in virus replication. Here, by using the online bioinformatics tools SRAMP and IF, we predict that the CVB3 genome contains m6A sites and found that CVB3 infection could alter the expression and cellular localization of m6A-related proteins. Moreover, we found that 3-deazaadenosine (3-DAA), an m6A modification inhibitor, significantly decreased CVB3 replication. We also observed that the m6A methyltransferases methyltransferase-like protein 3 (METTL3) and METTL14 play positive roles in CVB3 replication, whereas m6A demethylases fat mass and obesity-associated protein (FTO) or AlkB homolog 5 (ALKBH5) have opposite effects. Knockdown of the m6A binding proteins YTH domain family protein 1 (YTHDF1), YTHDF2 and YTHDF3 strikingly decreased CVB3 replication. Finally, the m6A site mutation in the CVB3 genome decreased the replication of CVB3 compared with that in the CVB3 wild-type (WT) strain. Taken together, our results demonstrated that CVB3 could exploit m6A modification to promote viral replication, which provides new insights into the mechanism of the interaction between CVB3 and the host.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muchen Zhang, Xinyan Xu, Luqiong Lv, Jinyan Luo, Temoor Ahmed, Waleed A. A. Alsakkaf, Hayssam M. Ali, Ji’an Bi, Chengqi Yan, Chunyan Gu, Linfei Shou, Bin Li
Xanthomonas oryzae pv. oryzae (Xoo) is a significant bacterial pathogen responsible for outbreaks of bacterial leaf blight in rice, posing a major threat to rice cultivation worldwide. Effective management of this pathogen is crucial for ensuring rice yield and food security. In this study, we identified and characterized a novel Xoo phage, ZP3, isolated from diseased rice leaves in Zhejiang, China, which may offer new insights into biocontrol strategies against Xoo and contribute to the development of innovative approaches to combat bacterial leaf blight. Transmission electron microscopy indicated that ZP3 had a short, non-contractile tail. Genome sequencing and bioinformatic analysis showed that ZP3 had a double-stranded DNA genome with a length of 44,713 bp, a G + C content of 52.2%, and 59 predicted genes, which was similar to other OP1-type Xoo phages belonging to the genus Xipdecavirus. ZP3’s endolysin LysZP was further studied for its bacteriolytic action, and the N-terminal transmembrane domain of LysZP is suggested to be a signal–arrest–release sequence that mediates the translocation of LysZP to the periplasm. Our study contributes to the understanding of phage–Xoo interactions and suggests that phage ZP3 and its endolysin LysZP could be developed into biocontrol agents against this phytopathogen.
{"title":"Genomic Characterization of Phage ZP3 and Its Endolysin LysZP with Antimicrobial Potential against Xanthomonas oryzae pv. oryzae","authors":"Muchen Zhang, Xinyan Xu, Luqiong Lv, Jinyan Luo, Temoor Ahmed, Waleed A. A. Alsakkaf, Hayssam M. Ali, Ji’an Bi, Chengqi Yan, Chunyan Gu, Linfei Shou, Bin Li","doi":"10.3390/v16091450","DOIUrl":"https://doi.org/10.3390/v16091450","url":null,"abstract":"Xanthomonas oryzae pv. oryzae (Xoo) is a significant bacterial pathogen responsible for outbreaks of bacterial leaf blight in rice, posing a major threat to rice cultivation worldwide. Effective management of this pathogen is crucial for ensuring rice yield and food security. In this study, we identified and characterized a novel Xoo phage, ZP3, isolated from diseased rice leaves in Zhejiang, China, which may offer new insights into biocontrol strategies against Xoo and contribute to the development of innovative approaches to combat bacterial leaf blight. Transmission electron microscopy indicated that ZP3 had a short, non-contractile tail. Genome sequencing and bioinformatic analysis showed that ZP3 had a double-stranded DNA genome with a length of 44,713 bp, a G + C content of 52.2%, and 59 predicted genes, which was similar to other OP1-type Xoo phages belonging to the genus Xipdecavirus. ZP3’s endolysin LysZP was further studied for its bacteriolytic action, and the N-terminal transmembrane domain of LysZP is suggested to be a signal–arrest–release sequence that mediates the translocation of LysZP to the periplasm. Our study contributes to the understanding of phage–Xoo interactions and suggests that phage ZP3 and its endolysin LysZP could be developed into biocontrol agents against this phytopathogen.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hepatitis C virus (HCV) infection is among the leading causes of cirrhosis and hepatocellular carcinoma. Knowledge of its prevalence and risk factors can help to effectively fight the virus. This study was the first to investigate the seroprevalence of HCV, its genotypes, and factors associated with it among the general adult population of Armenia selected countrywide via cluster sampling. Anti-HCV antibodies were detected using third-generation immunoassay. Polymerase chain reaction and genotyping was performed among anti-HCV-positive individuals. Shortly after testing, the participants underwent a telephone survey. Logistic regression models were fitted to identify factors associated with anti-HCV antibody positivity and chronic HCV infection. The prevalence of anti-HCV antibodies among 3831 tested individuals was 2% (99% CI 1.4, 2.5), and chronic HCV infection was 0.7% (99% CI 0.4, 1.0), with genotypes 3 and 2 being the most common. The risk factors for chronic HCV infection included self-reported chronic liver disease (95% CI 1.47, 15.28), having tattoos (95% CI 1.34, 10.94), ever smoking (95% CI 1.16, 9.18), and testing positive for hepatitis B virus core antibody (95% CI 1.02, 7.17). These risk factors demonstrate that there could be room for strengthening infection control measures to prevent the transmission of HCV in Armenia.
丙型肝炎病毒（HCV）感染是导致肝硬化和肝细胞癌的主要原因之一。了解丙型肝炎病毒的流行情况和风险因素有助于有效地抗击该病毒。本研究首次调查了亚美尼亚全国范围内通过集群抽样选取的普通成年人群中的丙型肝炎病毒（HCV）血清流行率、基因型及相关因素。采用第三代免疫测定法检测抗 HCV 抗体。对抗-HCV 阳性者进行聚合酶链反应和基因分型。检测后不久，参与者接受了电话调查。为确定与抗-HCV 抗体阳性和慢性 HCV 感染相关的因素，对 Logistic 回归模型进行了拟合。在接受检测的 3831 人中，抗 HCV 抗体阳性率为 2%（99% CI 1.4，2.5），慢性 HCV 感染率为 0.7%（99% CI 0.4，1.0），其中基因型 3 和 2 最为常见。慢性 HCV 感染的风险因素包括自我报告的慢性肝病（95% CI 1.47，15.28）、有纹身（95% CI 1.34，10.94）、曾经吸烟（95% CI 1.16，9.18）以及乙型肝炎病毒核心抗体检测呈阳性（95% CI 1.02，7.17）。这些风险因素表明，亚美尼亚仍有加强感染控制措施以预防丙型肝炎病毒传播的余地。
{"title":"Seroprevalence of Hepatitis C Virus and Factors Associated with It in Armenia, 2021","authors":"Anahit Demirchyan, Antons Mozalevskis, Serine Sahakyan, Lusine Musheghyan, Lusine Aslanyan, Diana Muradyan, Narina Sargsyants, Gayane Ghukasyan, Varduhi Petrosyan","doi":"10.3390/v16091446","DOIUrl":"https://doi.org/10.3390/v16091446","url":null,"abstract":"Hepatitis C virus (HCV) infection is among the leading causes of cirrhosis and hepatocellular carcinoma. Knowledge of its prevalence and risk factors can help to effectively fight the virus. This study was the first to investigate the seroprevalence of HCV, its genotypes, and factors associated with it among the general adult population of Armenia selected countrywide via cluster sampling. Anti-HCV antibodies were detected using third-generation immunoassay. Polymerase chain reaction and genotyping was performed among anti-HCV-positive individuals. Shortly after testing, the participants underwent a telephone survey. Logistic regression models were fitted to identify factors associated with anti-HCV antibody positivity and chronic HCV infection. The prevalence of anti-HCV antibodies among 3831 tested individuals was 2% (99% CI 1.4, 2.5), and chronic HCV infection was 0.7% (99% CI 0.4, 1.0), with genotypes 3 and 2 being the most common. The risk factors for chronic HCV infection included self-reported chronic liver disease (95% CI 1.47, 15.28), having tattoos (95% CI 1.34, 10.94), ever smoking (95% CI 1.16, 9.18), and testing positive for hepatitis B virus core antibody (95% CI 1.02, 7.17). These risk factors demonstrate that there could be room for strengthening infection control measures to prevent the transmission of HCV in Armenia.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Krannich, Dimitri Ternovoj, Sofia Paraskevopoulou, Stephan Fuchs
The identification of genomic variants has become a routine task in the age of genome sequencing. In particular, small genomic variants of a single or few nucleotides are routinely investigated for their impact on an organism’s phenotype. Hence, the precise and robust detection of the variants’ exact genomic locations and changes in nucleotide composition is vital in many biological applications. Although a plethora of methods exist for the many key steps of variant detection, thoroughly testing the detection process and evaluating its results is still a cumbersome procedure. In this work, we present a collection of easy-to-apply and highly modifiable workflows to facilitate the generation of synthetic test data, as well as to evaluate the accordance of a user-provided set of variants with the test data. The workflows are implemented in Nextflow and are open-source and freely available on Github under the GPL-3.0 license.
{"title":"CIEVaD: A Lightweight Workflow Collection for the Rapid and On-Demand Deployment of End-to-End Testing for Genomic Variant Detection","authors":"Thomas Krannich, Dimitri Ternovoj, Sofia Paraskevopoulou, Stephan Fuchs","doi":"10.3390/v16091444","DOIUrl":"https://doi.org/10.3390/v16091444","url":null,"abstract":"The identification of genomic variants has become a routine task in the age of genome sequencing. In particular, small genomic variants of a single or few nucleotides are routinely investigated for their impact on an organism’s phenotype. Hence, the precise and robust detection of the variants’ exact genomic locations and changes in nucleotide composition is vital in many biological applications. Although a plethora of methods exist for the many key steps of variant detection, thoroughly testing the detection process and evaluating its results is still a cumbersome procedure. In this work, we present a collection of easy-to-apply and highly modifiable workflows to facilitate the generation of synthetic test data, as well as to evaluate the accordance of a user-provided set of variants with the test data. The workflows are implemented in Nextflow and are open-source and freely available on Github under the GPL-3.0 license.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aleksandra Kozieł, Aleksandra Cieślik, Łucja Janek, Aleksandra Szymczak, Igor Domański, Brygida Knysz, Bartosz Szetela
The HIV (Human Immunodeficiency Virus) epidemic remains a significant public health issue, requiring ongoing access to preventive methods. This study aimed to analyze the evolution of the HIV epidemic in Lower Silesia from 2010 to 2020, focusing on the key populations. A retrospective analysis of the medical records from newly diagnosed HIV patients at a major HIV clinic in Wroclaw was conducted, examining demographic data, infection routes, and laboratory results. An 84% increase in newly diagnosed HIV cases was observed over the decade, with the most common route of infection being sex between men (70% among those with a known infection route). These patients were generally in better clinical condition compared to their heterosexual counterparts, as indicated by a higher median CD4+ T cell count (465/μL vs. 250/μL). The changes in clinical status and infection routes were statistically significant. The HIV epidemic in Lower Silesia has shifted, with a notable rise in new infections among men who have sex with men. Heterosexual patients were often diagnosed at more advanced stages. Prevention strategies should adapt to these changing trends, with education and testing accessibility remaining priorities nationwide.
{"title":"Changes in the HIV Epidemic in Lower Silesia, Poland, Between 2010 and 2020: The Characteristics of the Key Populations","authors":"Aleksandra Kozieł, Aleksandra Cieślik, Łucja Janek, Aleksandra Szymczak, Igor Domański, Brygida Knysz, Bartosz Szetela","doi":"10.3390/v16091445","DOIUrl":"https://doi.org/10.3390/v16091445","url":null,"abstract":"The HIV (Human Immunodeficiency Virus) epidemic remains a significant public health issue, requiring ongoing access to preventive methods. This study aimed to analyze the evolution of the HIV epidemic in Lower Silesia from 2010 to 2020, focusing on the key populations. A retrospective analysis of the medical records from newly diagnosed HIV patients at a major HIV clinic in Wroclaw was conducted, examining demographic data, infection routes, and laboratory results. An 84% increase in newly diagnosed HIV cases was observed over the decade, with the most common route of infection being sex between men (70% among those with a known infection route). These patients were generally in better clinical condition compared to their heterosexual counterparts, as indicated by a higher median CD4+ T cell count (465/μL vs. 250/μL). The changes in clinical status and infection routes were statistically significant. The HIV epidemic in Lower Silesia has shifted, with a notable rise in new infections among men who have sex with men. Heterosexual patients were often diagnosed at more advanced stages. Prevention strategies should adapt to these changing trends, with education and testing accessibility remaining priorities nationwide.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoying Cai, Kang Zhou, Ana Lucia Alvarez-Cabrera, Zhu Si, Hui Wang, Yao He, Cally Li, Z. Hong Zhou
Rabies virus (RABV) is among the first recognized viruses of public health concern and has historically contributed to the development of viral vaccines. Despite these significances, the three-dimensional structure of the RABV virion remains unknown due to the challenges in isolating structurally homogenous virion samples in sufficient quantities needed for structural investigation. Here, by combining the capabilities of cryogenic electron tomography (cryoET) and microscopy (cryoEM), we determined the three-dimensional structure of the wild-type RABV virion. Tomograms of RABV virions reveal a high level of structural heterogeneity among the bullet-shaped virion particles encompassing the glycoprotein (G) trimer-decorated envelope and the nucleocapsid composed of RNA, nucleoprotein (N), and matrix protein (M). The structure of the trunk region of the virion was determined by cryoEM helical reconstruction, revealing a one-start N-RNA helix bound by a single layer of M proteins at an N:M ratio of 1. The N-M interaction differs from that in fellow rhabdovirus vesicular stomatitis virus (VSV), which features two layers of M stabilizing the N-RNA helix at an M:N ratio of 2. These differences in both M-N stoichiometry and binding allow RABV to flex its N-RNA helix more freely and point to different mechanisms of viral assembly between these two bullet-shaped rhabdoviruses.
狂犬病病毒（RABV）是最早被确认的公共卫生问题病毒之一，并在历史上为病毒疫苗的开发做出了贡献。尽管具有这些重要意义，但 RABV 病毒的三维结构仍然不为人知，这是因为要分离出足够数量的结构均一的病毒样本进行结构研究是一项挑战。在这里，我们结合低温电子断层扫描（cryoET）和显微镜（cryoEM）的功能，确定了野生型 RABV 病毒的三维结构。RABV 病毒的断层图显示，子弹头形病毒粒子的结构具有高度异质性，包括糖蛋白（G）三聚体装饰的包膜和由 RNA、核蛋白（N）和基质蛋白（M）组成的核头皮。通过冷冻电镜螺旋重建确定了病毒躯干区的结构，发现一个由单层 M 蛋白结合的单起始 N-RNA 螺旋，N:M 比为 1；N-M 相互作用与同属横纹肌病毒的水泡性口炎病毒（VSV）不同，后者有两层 M 蛋白稳定 N-RNA 螺旋，M:N 比为 2。M-N比例和结合的这些差异使RABV能够更自由地弯曲其N-RNA螺旋，并表明这两种子弹形横纹肌病毒的病毒组装机制不同。
{"title":"Structural Heterogeneity of the Rabies Virus Virion","authors":"Xiaoying Cai, Kang Zhou, Ana Lucia Alvarez-Cabrera, Zhu Si, Hui Wang, Yao He, Cally Li, Z. Hong Zhou","doi":"10.3390/v16091447","DOIUrl":"https://doi.org/10.3390/v16091447","url":null,"abstract":"Rabies virus (RABV) is among the first recognized viruses of public health concern and has historically contributed to the development of viral vaccines. Despite these significances, the three-dimensional structure of the RABV virion remains unknown due to the challenges in isolating structurally homogenous virion samples in sufficient quantities needed for structural investigation. Here, by combining the capabilities of cryogenic electron tomography (cryoET) and microscopy (cryoEM), we determined the three-dimensional structure of the wild-type RABV virion. Tomograms of RABV virions reveal a high level of structural heterogeneity among the bullet-shaped virion particles encompassing the glycoprotein (G) trimer-decorated envelope and the nucleocapsid composed of RNA, nucleoprotein (N), and matrix protein (M). The structure of the trunk region of the virion was determined by cryoEM helical reconstruction, revealing a one-start N-RNA helix bound by a single layer of M proteins at an N:M ratio of 1. The N-M interaction differs from that in fellow rhabdovirus vesicular stomatitis virus (VSV), which features two layers of M stabilizing the N-RNA helix at an M:N ratio of 2. These differences in both M-N stoichiometry and binding allow RABV to flex its N-RNA helix more freely and point to different mechanisms of viral assembly between these two bullet-shaped rhabdoviruses.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Camille Wouters, Jaiprasath Sachithanandham, Elgin Akin, Lisa Pieterse, Amary Fall, Thao T. Truong, Jennifer Dien Bard, Rebecca Yee, David J. Sullivan, Heba H. Mostafa, Andrew Pekosz
SARS-CoV-2 infection of immunocompromised individuals often leads to prolonged detection of viral RNA and infectious virus in nasal specimens, presumably due to the lack of induction of an appropriate adaptive immune response. Mutations identified in virus sequences obtained from persistently infected patients bear signatures of immune evasion and have some overlap with sequences present in variants of concern. We characterized virus isolates obtained greater than 100 days after the initial COVID-19 diagnosis from two COVID-19 patients undergoing immunosuppressive cancer therapy, wand compared them to an isolate from the start of the infection. Isolates from an individual who never mounted an antibody response specific to SARS-CoV-2 despite the administration of convalescent plasma showed slight reductions in plaque size and some showed temperature-dependent replication attenuation on human nasal epithelial cell culture compared to the virus that initiated infection. An isolate from another patient—who did mount a SARS-CoV-2 IgM response—showed temperature-dependent changes in plaque size as well as increased syncytia formation and escape from serum-neutralizing antibodies. Our results indicate that not all virus isolates from immunocompromised COVID-19 patients display clear signs of phenotypic change, but increased attention should be paid to monitoring virus evolution in this patient population.
{"title":"SARS-CoV-2 Variants from Long-Term, Persistently Infected Immunocompromised Patients Have Altered Syncytia Formation, Temperature-Dependent Replication, and Serum Neutralizing Antibody Escape","authors":"Camille Wouters, Jaiprasath Sachithanandham, Elgin Akin, Lisa Pieterse, Amary Fall, Thao T. Truong, Jennifer Dien Bard, Rebecca Yee, David J. Sullivan, Heba H. Mostafa, Andrew Pekosz","doi":"10.3390/v16091436","DOIUrl":"https://doi.org/10.3390/v16091436","url":null,"abstract":"SARS-CoV-2 infection of immunocompromised individuals often leads to prolonged detection of viral RNA and infectious virus in nasal specimens, presumably due to the lack of induction of an appropriate adaptive immune response. Mutations identified in virus sequences obtained from persistently infected patients bear signatures of immune evasion and have some overlap with sequences present in variants of concern. We characterized virus isolates obtained greater than 100 days after the initial COVID-19 diagnosis from two COVID-19 patients undergoing immunosuppressive cancer therapy, wand compared them to an isolate from the start of the infection. Isolates from an individual who never mounted an antibody response specific to SARS-CoV-2 despite the administration of convalescent plasma showed slight reductions in plaque size and some showed temperature-dependent replication attenuation on human nasal epithelial cell culture compared to the virus that initiated infection. An isolate from another patient—who did mount a SARS-CoV-2 IgM response—showed temperature-dependent changes in plaque size as well as increased syncytia formation and escape from serum-neutralizing antibodies. Our results indicate that not all virus isolates from immunocompromised COVID-19 patients display clear signs of phenotypic change, but increased attention should be paid to monitoring virus evolution in this patient population.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：