The last thirty years have seen a meteoric rise in the number of sequenced bacteriophage genomes, spurred on by both the rise and success of groups working to isolate and characterize phages, and the rapid and significant technological improvements and reduced costs associated with sequencing their genomes. Over the course of these decades, the tools used to glean evolutionary insights from these sequences have grown more complex and sophisticated, and we describe here the suite of computational and bioinformatic tools used extensively by the integrated research–education communities such as SEA-PHAGES and PHIRE, which are jointly responsible for 25% of all complete phage genomes in the RefSeq database. These tools are used to integrate and analyze phage genome data from different sources, for identification and precise extraction of prophages from bacterial genomes, computing “phamilies” of related genes, and displaying the complex nucleotide and amino acid level mosaicism of these genomes. While over 50,000 SEA-PHAGES students have primarily benefitted from these tools, they are freely available for the phage community at large.
{"title":"A Bioinformatic Ecosystem for Bacteriophage Genomics: PhaMMSeqs, Phamerator, pdm_utils, PhagesDB, DEPhT, and PhamClust","authors":"Christian H. Gauthier, Graham F. Hatfull","doi":"10.3390/v16081278","DOIUrl":"https://doi.org/10.3390/v16081278","url":null,"abstract":"The last thirty years have seen a meteoric rise in the number of sequenced bacteriophage genomes, spurred on by both the rise and success of groups working to isolate and characterize phages, and the rapid and significant technological improvements and reduced costs associated with sequencing their genomes. Over the course of these decades, the tools used to glean evolutionary insights from these sequences have grown more complex and sophisticated, and we describe here the suite of computational and bioinformatic tools used extensively by the integrated research–education communities such as SEA-PHAGES and PHIRE, which are jointly responsible for 25% of all complete phage genomes in the RefSeq database. These tools are used to integrate and analyze phage genome data from different sources, for identification and precise extraction of prophages from bacterial genomes, computing “phamilies” of related genes, and displaying the complex nucleotide and amino acid level mosaicism of these genomes. While over 50,000 SEA-PHAGES students have primarily benefitted from these tools, they are freely available for the phage community at large.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141932105","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}
Interactions between human immunodeficiency virus type 1 (HIV-1) and the host factors or restriction factors of its target cells determine the cell’s susceptibility to, and outcome of, infection. Factors intrinsic to the cell are involved at every step of the HIV-1 replication cycle, contributing to productive infection and replication, or severely attenuating the chances of success. Furthermore, factors unique to certain cell types contribute to the differences in infection between these cell types. Understanding the involvement of these factors in HIV-1 infection is a key requirement for the development of anti-HIV-1 therapies. As the list of factors grows, and the dynamic interactions between these factors and the virus are elucidated, comprehensive and up-to-date summaries that recount the knowledge gathered after decades of research are beneficial to the field, displaying what is known so that researchers can build off the groundwork of others to investigate what is unknown. Herein, we aim to provide a review focusing on protein host factors, both well-known and relatively new, that impact HIV-1 replication in a positive or negative manner at each stage of the replication cycle, highlighting factors unique to the various HIV-1 target cell types where appropriate.
{"title":"Help or Hinder: Protein Host Factors That Impact HIV-1 Replication","authors":"Michael Rameen Moezpoor, Mario Stevenson","doi":"10.3390/v16081281","DOIUrl":"https://doi.org/10.3390/v16081281","url":null,"abstract":"Interactions between human immunodeficiency virus type 1 (HIV-1) and the host factors or restriction factors of its target cells determine the cell’s susceptibility to, and outcome of, infection. Factors intrinsic to the cell are involved at every step of the HIV-1 replication cycle, contributing to productive infection and replication, or severely attenuating the chances of success. Furthermore, factors unique to certain cell types contribute to the differences in infection between these cell types. Understanding the involvement of these factors in HIV-1 infection is a key requirement for the development of anti-HIV-1 therapies. As the list of factors grows, and the dynamic interactions between these factors and the virus are elucidated, comprehensive and up-to-date summaries that recount the knowledge gathered after decades of research are beneficial to the field, displaying what is known so that researchers can build off the groundwork of others to investigate what is unknown. Herein, we aim to provide a review focusing on protein host factors, both well-known and relatively new, that impact HIV-1 replication in a positive or negative manner at each stage of the replication cycle, highlighting factors unique to the various HIV-1 target cell types where appropriate.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141932223","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}
Monty E. Goldstein, Maxinne A. Ignacio, Jeffrey M. Loube, Matthew R. Whorton, Margaret A. Scull
Rhinovirus C (RV-C) infects airway epithelial cells and is an important cause of acute respiratory disease in humans. To interrogate the mechanisms of RV-C-mediated disease, animal models are essential. Towards this, RV-C infection was recently reported in wild-type (WT) mice, yet, titers were not sustained. Therefore, the requirements for RV-C infection in mice remain unclear. Notably, prior work has implicated human cadherin-related family member 3 (CDHR3) and stimulator of interferon genes (STING) as essential host factors for virus uptake and replication, respectively. Here, we report that even though human (h) and murine (m) CDHR3 orthologs have similar tissue distribution, amino acid sequence homology is limited. Further, while RV-C can replicate in mouse lung epithelial type 1 (LET1) cells and produce infectious virus, we observed a significant increase in the frequency and intensity of dsRNA-positive cells following hSTING expression. Based on these findings, we sought to assess the impact of hCDHR3 and hSTING on RV-C infection in mice in vivo. Thus, we developed hCDHR3 transgenic mice, and utilized adeno-associated virus (AAV) to deliver hSTING to the murine airways. Subsequent challenge of these mice with RV-C15 revealed significantly higher titers 24 h post-infection in mice expressing both hCDHR3 and hSTING—compared to either WT mice, or mice with hCDHR3 or hSTING alone, indicating more efficient infection. Ultimately, this mouse model can be further engineered to establish a robust in vivo model, recapitulating viral dynamics and disease.
{"title":"Human Stimulator of Interferon Genes Promotes Rhinovirus C Replication in Mouse Cells In Vitro and In Vivo","authors":"Monty E. Goldstein, Maxinne A. Ignacio, Jeffrey M. Loube, Matthew R. Whorton, Margaret A. Scull","doi":"10.3390/v16081282","DOIUrl":"https://doi.org/10.3390/v16081282","url":null,"abstract":"Rhinovirus C (RV-C) infects airway epithelial cells and is an important cause of acute respiratory disease in humans. To interrogate the mechanisms of RV-C-mediated disease, animal models are essential. Towards this, RV-C infection was recently reported in wild-type (WT) mice, yet, titers were not sustained. Therefore, the requirements for RV-C infection in mice remain unclear. Notably, prior work has implicated human cadherin-related family member 3 (CDHR3) and stimulator of interferon genes (STING) as essential host factors for virus uptake and replication, respectively. Here, we report that even though human (h) and murine (m) CDHR3 orthologs have similar tissue distribution, amino acid sequence homology is limited. Further, while RV-C can replicate in mouse lung epithelial type 1 (LET1) cells and produce infectious virus, we observed a significant increase in the frequency and intensity of dsRNA-positive cells following hSTING expression. Based on these findings, we sought to assess the impact of hCDHR3 and hSTING on RV-C infection in mice in vivo. Thus, we developed hCDHR3 transgenic mice, and utilized adeno-associated virus (AAV) to deliver hSTING to the murine airways. Subsequent challenge of these mice with RV-C15 revealed significantly higher titers 24 h post-infection in mice expressing both hCDHR3 and hSTING—compared to either WT mice, or mice with hCDHR3 or hSTING alone, indicating more efficient infection. Ultimately, this mouse model can be further engineered to establish a robust in vivo model, recapitulating viral dynamics and disease.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141932210","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}
The objective of this study was to analyze the epidemiological links of the human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HIV-HCV coinfections to less studied types of transmission in certain populations. We performed an observational, prospective study on 903 patients aged between 15–87 years who took part in the Open Test Project. They were divided in two subgroups: general population vs. individuals from prisons who were questioned about multiple risk factors. A chi-square independence test was used to establish correlations between risk factors and results of screening tests. Logistic regression was used to calculate the probability of a reactive screening test based on each independent risk factor and age. HIV was very strongly associated with unprotected sexual intercourse with HIV-positive partners (the strongest association), unprotected sexual intercourse with sex workers, newly diagnosed sexually transmitted diseases (STDs), intravenous drug users (IDUs) and sharing injecting materials. In the case of HCV reactive tests, very strong associations have been established with IDUs (the strongest association), unprotected sex with IDUs and sharing injecting materials. Our study indicates the need for implementing targeted public health programs, tailored to the local epidemiology that can ultimately lead to micro-elimination of hepatitis and HIV infections in this area.
{"title":"HIV, HCV and HIV-HCV Coinfections in the General Population versus Inmates from Romania","authors":"Camelia Sultana, Carmine Falanga, Grațiana Chicin, Laurențiu Ion, Camelia Grancea, Daniela Chiriac, Adriana Iliescu, Andrea Gori","doi":"10.3390/v16081279","DOIUrl":"https://doi.org/10.3390/v16081279","url":null,"abstract":"The objective of this study was to analyze the epidemiological links of the human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HIV-HCV coinfections to less studied types of transmission in certain populations. We performed an observational, prospective study on 903 patients aged between 15–87 years who took part in the Open Test Project. They were divided in two subgroups: general population vs. individuals from prisons who were questioned about multiple risk factors. A chi-square independence test was used to establish correlations between risk factors and results of screening tests. Logistic regression was used to calculate the probability of a reactive screening test based on each independent risk factor and age. HIV was very strongly associated with unprotected sexual intercourse with HIV-positive partners (the strongest association), unprotected sexual intercourse with sex workers, newly diagnosed sexually transmitted diseases (STDs), intravenous drug users (IDUs) and sharing injecting materials. In the case of HCV reactive tests, very strong associations have been established with IDUs (the strongest association), unprotected sex with IDUs and sharing injecting materials. Our study indicates the need for implementing targeted public health programs, tailored to the local epidemiology that can ultimately lead to micro-elimination of hepatitis and HIV infections in this area.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141932131","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}
Lindsey R. Riback, Mercy Nyakowa, John A. Lizcano, Chenshu Zhang, Peter Cherutich, Ann E. Kurth, Matthew J. Akiyama
Polysubstance use (PSU), injection drug use (IDU), and equipment sharing are associated with bloodborne infection (BBI) transmission risk, particularly Hepatitis C Virus (HCV), yet data on PSU in low- and middle-income countries (LMICs) is limited. We report on baseline PSU, medication-assisted treatment (MAT) engagement, and motivation to reduce IDU among 95 people who inject drugs (PWID) who accessed needle and syringe programs (NSP) in Nairobi and Coastal Kenya prior to HCV treatment. Bivariate and multivariate logistic regression were used to examine the associations between PSU and behaviors that confer HCV transmission and acquisition risks. Most participants (70.5%) reported PSU in the last 30 days, and one-third (35.8%) reported PSU exclusive to just heroin and cannabis use. Common combinations were heroin and cannabis (49.3%), and heroin, cannabis, and bugizi (flunitrazepam) (29.9%). Participants at baseline were receiving MAT (69.5%), already stopped or reduced IDU (30.5%), and were HIV-positive (40%). PSU was significantly associated with IDU (p = 0.008) and the number of times (p = 0.016) and days (p = 0.007) injected in the last 30 days. Participants reported high PSU and equipment sharing, despite high MAT engagement. While co-locating BBI treatment within existing harm reduction services is necessary to promote uptake and curb re-infection, tailored services may be needed to address PSU, particularly in LMICs.
{"title":"Polysubstance Use and Related Risk Behaviors among People Who Inject Drugs in Kenya Preparing for Hepatitis C Virus Treatment","authors":"Lindsey R. Riback, Mercy Nyakowa, John A. Lizcano, Chenshu Zhang, Peter Cherutich, Ann E. Kurth, Matthew J. Akiyama","doi":"10.3390/v16081277","DOIUrl":"https://doi.org/10.3390/v16081277","url":null,"abstract":"Polysubstance use (PSU), injection drug use (IDU), and equipment sharing are associated with bloodborne infection (BBI) transmission risk, particularly Hepatitis C Virus (HCV), yet data on PSU in low- and middle-income countries (LMICs) is limited. We report on baseline PSU, medication-assisted treatment (MAT) engagement, and motivation to reduce IDU among 95 people who inject drugs (PWID) who accessed needle and syringe programs (NSP) in Nairobi and Coastal Kenya prior to HCV treatment. Bivariate and multivariate logistic regression were used to examine the associations between PSU and behaviors that confer HCV transmission and acquisition risks. Most participants (70.5%) reported PSU in the last 30 days, and one-third (35.8%) reported PSU exclusive to just heroin and cannabis use. Common combinations were heroin and cannabis (49.3%), and heroin, cannabis, and bugizi (flunitrazepam) (29.9%). Participants at baseline were receiving MAT (69.5%), already stopped or reduced IDU (30.5%), and were HIV-positive (40%). PSU was significantly associated with IDU (p = 0.008) and the number of times (p = 0.016) and days (p = 0.007) injected in the last 30 days. Participants reported high PSU and equipment sharing, despite high MAT engagement. While co-locating BBI treatment within existing harm reduction services is necessary to promote uptake and curb re-infection, tailored services may be needed to address PSU, particularly in LMICs.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141932102","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}
Oumarou Soro, Collins Kigen, A. Nyerere, Moses Gachoya, Martin Georges, Erick Odoyo, L. Musila
Enterococcus faecalis (E. faecalis) is a growing cause of nosocomial and antibiotic-resistant infections. Treating drug-resistant E. faecalis requires novel approaches. The use of bacteriophages (phages) against multidrug-resistant (MDR) bacteria has recently garnered global attention. Biofilms play a vital role in E. faecalis pathogenesis as they enhance antibiotic resistance. Phages eliminate biofilms by producing lytic enzymes, including depolymerases. In this study, Enterococcus phage vB_Efs8_KEN04, isolated from a sewage treatment plant in Nairobi, Kenya, was tested against clinical strains of MDR E. faecalis. This phage had a broad host range against 100% (26/26) of MDR E. faecalis clinical isolates and cross-species activity against Enterococcus faecium. It was able to withstand acidic and alkaline conditions, from pH 3 to 11, as well as temperatures between −80 °C and 37 °C. It could inhibit and disrupt the biofilms of MDR E. faecalis. Its linear double-stranded DNA genome of 142,402 bp contains 238 coding sequences with a G + C content and coding gene density of 36.01% and 91.46%, respectively. Genomic analyses showed that phage vB_Efs8_KEN04 belongs to the genus Kochikohdavirus in the family Herelleviridae. It lacked antimicrobial resistance, virulence, and lysogeny genes, and its stability, broad host range, and cross-species lysis indicate strong potential for the treatment of Enterococcus infections.
粪肠球菌（Enterococcus faecalis，E. faecalis）是造成医院内感染和耐抗生素感染的一个日益严重的原因。治疗耐药粪肠球菌需要新的方法。使用噬菌体（phages）来对付耐多药（MDR）细菌最近引起了全球关注。生物膜在粪大肠杆菌的致病过程中起着至关重要的作用，因为生物膜会增强抗生素耐药性。噬菌体通过产生溶解酶（包括解聚酶）来消除生物膜。在这项研究中，从肯尼亚内罗毕污水处理厂分离出来的肠球菌噬菌体 vB_Efs8_KEN04 针对 MDR 粪绿球菌的临床菌株进行了测试。该噬菌体对 100%（26/26）的 MDR 粪肠球菌临床分离株具有广泛的宿主范围，对粪肠球菌具有跨物种活性。它能够耐受 pH 值为 3 至 11 的酸性和碱性条件，以及 -80 °C 至 37 °C 的温度。它能抑制和破坏 MDR 粪肠球菌的生物膜。它的线性双链 DNA 基因组长达 142 402 bp，包含 238 个编码序列，G + C 含量和编码基因密度分别为 36.01% 和 91.46%。基因组分析表明，vB_Efs8_KEN04噬菌体属于Herelleviridae科Kochikohdavirus属。它缺乏抗菌素抗性、毒力和裂解基因，其稳定性、广泛的宿主范围和跨物种裂解表明它具有治疗肠球菌感染的强大潜力。
{"title":"Characterization and Anti-Biofilm Activity of Lytic Enterococcus Phage vB_Efs8_KEN04 against Clinical Isolates of Multidrug-Resistant Enterococcus faecalis in Kenya","authors":"Oumarou Soro, Collins Kigen, A. Nyerere, Moses Gachoya, Martin Georges, Erick Odoyo, L. Musila","doi":"10.3390/v16081275","DOIUrl":"https://doi.org/10.3390/v16081275","url":null,"abstract":"Enterococcus faecalis (E. faecalis) is a growing cause of nosocomial and antibiotic-resistant infections. Treating drug-resistant E. faecalis requires novel approaches. The use of bacteriophages (phages) against multidrug-resistant (MDR) bacteria has recently garnered global attention. Biofilms play a vital role in E. faecalis pathogenesis as they enhance antibiotic resistance. Phages eliminate biofilms by producing lytic enzymes, including depolymerases. In this study, Enterococcus phage vB_Efs8_KEN04, isolated from a sewage treatment plant in Nairobi, Kenya, was tested against clinical strains of MDR E. faecalis. This phage had a broad host range against 100% (26/26) of MDR E. faecalis clinical isolates and cross-species activity against Enterococcus faecium. It was able to withstand acidic and alkaline conditions, from pH 3 to 11, as well as temperatures between −80 °C and 37 °C. It could inhibit and disrupt the biofilms of MDR E. faecalis. Its linear double-stranded DNA genome of 142,402 bp contains 238 coding sequences with a G + C content and coding gene density of 36.01% and 91.46%, respectively. Genomic analyses showed that phage vB_Efs8_KEN04 belongs to the genus Kochikohdavirus in the family Herelleviridae. It lacked antimicrobial resistance, virulence, and lysogeny genes, and its stability, broad host range, and cross-species lysis indicate strong potential for the treatment of Enterococcus infections.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141923670","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}
Pigs are the most common amplifying hosts of the Japanese encephalitis virus (JEV). In 2016, four residents on Tsushima Island who did not own pig farms were diagnosed with JE. Therefore, a serosurvey was conducted to estimate the risk and seroprevalence of JEV after the outbreak. Sera collected from 560 Tsushima Island residents between January and September 2017 were tested for neutralizing antibodies against JEV strains JaGAr01 (genotype 3) and Muar (genotype 5). Sera collected from six wild boars between June and July 2022 were tested. The seroprevalence rates of neutralizing antibodies against JaGAr01 and Muar were 38.8% and 24.6%, respectively. High anti-JEV neutralizing antibody titers of ≥320 were identified in 16 residents, including 3 younger than 6 years with prior JEV vaccination, 2 in their 40s, and 11 older than 70. However, no anti-JEV-specific IgM was detected. Residents who engaged in outdoor activities had higher anti-JEV antibody titers. Sera from wild boars were negative for JEV RNA, but four of six samples contained neutralizing antibodies against JEV. Therefore, JEV transmission continues on Tsushima Island, even in the absence of pig farms, and wild boars might serve as the amplifying hosts.
{"title":"The Role of Wild Boar as Host of Japanese Encephalitis Virus in the Absence of Domestic Pigs","authors":"Fuka Kikuchi, Ai Hayashi, Karen Yamada, Yusuke Matsui, Reiko Shimbashi, Yuji Noguchi, Kazunori Tachibana, Tetsuya Mizutani, Akihiko Tokaji, Akira Yoshikawa, Motoki Ihara, Kazunori Oishi, Hajime Kamiya, Satoru Arai, Motoi Suzuki","doi":"10.3390/v16081273","DOIUrl":"https://doi.org/10.3390/v16081273","url":null,"abstract":"Pigs are the most common amplifying hosts of the Japanese encephalitis virus (JEV). In 2016, four residents on Tsushima Island who did not own pig farms were diagnosed with JE. Therefore, a serosurvey was conducted to estimate the risk and seroprevalence of JEV after the outbreak. Sera collected from 560 Tsushima Island residents between January and September 2017 were tested for neutralizing antibodies against JEV strains JaGAr01 (genotype 3) and Muar (genotype 5). Sera collected from six wild boars between June and July 2022 were tested. The seroprevalence rates of neutralizing antibodies against JaGAr01 and Muar were 38.8% and 24.6%, respectively. High anti-JEV neutralizing antibody titers of ≥320 were identified in 16 residents, including 3 younger than 6 years with prior JEV vaccination, 2 in their 40s, and 11 older than 70. However, no anti-JEV-specific IgM was detected. Residents who engaged in outdoor activities had higher anti-JEV antibody titers. Sera from wild boars were negative for JEV RNA, but four of six samples contained neutralizing antibodies against JEV. Therefore, JEV transmission continues on Tsushima Island, even in the absence of pig farms, and wild boars might serve as the amplifying hosts.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141923474","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}
Viruses are obligate intracellular pathogens as their replication depends on the metabolism of the host cell. The induction of cellular suicide, known as programmed cell death (PCD), has the potential to hinder viral replication and act as a first line of defense against viral pathogens. Apoptosis, necroptosis, and pyroptosis are three important PCD modalities. Different signaling pathways are involved in their execution, and they also differ in their ability to cause inflammation. Cytomegaloviruses (CMV), beta-herpesviruses with large double-stranded DNA genomes, encode a great variety of immune evasion genes, including several cell death suppressors. While CMV inhibitors of apoptosis and necroptosis have been known and studied for years, the first pyroptosis inhibitor has been identified and characterized only recently. Here, we describe how human and murine CMV interfere with apoptosis, necroptosis, and pyroptosis signaling pathways. We also discuss the importance of the different PCD forms and their viral inhibitors for the containment of viral replication and spread in vivo.
{"title":"No Time to Die: How Cytomegaloviruses Suppress Apoptosis, Necroptosis, and Pyroptosis","authors":"Yingqi Deng, Ana Águeda-Pinto, W. Brune","doi":"10.3390/v16081272","DOIUrl":"https://doi.org/10.3390/v16081272","url":null,"abstract":"Viruses are obligate intracellular pathogens as their replication depends on the metabolism of the host cell. The induction of cellular suicide, known as programmed cell death (PCD), has the potential to hinder viral replication and act as a first line of defense against viral pathogens. Apoptosis, necroptosis, and pyroptosis are three important PCD modalities. Different signaling pathways are involved in their execution, and they also differ in their ability to cause inflammation. Cytomegaloviruses (CMV), beta-herpesviruses with large double-stranded DNA genomes, encode a great variety of immune evasion genes, including several cell death suppressors. While CMV inhibitors of apoptosis and necroptosis have been known and studied for years, the first pyroptosis inhibitor has been identified and characterized only recently. Here, we describe how human and murine CMV interfere with apoptosis, necroptosis, and pyroptosis signaling pathways. We also discuss the importance of the different PCD forms and their viral inhibitors for the containment of viral replication and spread in vivo.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141921703","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}
Petrus Jansen van Vuren, Rhys H. Parry, J. T. Pawęska
In July 2017, a family of three members, a 46-year-old male, a 45-year-old female and their 8-year-old daughter, returned to South Africa from Thailand. They presented symptoms consistent with mosquito-borne diseases, including fever, headache, severe body aches and nausea. Mosquito bites in all family members suggested recent exposure to arthropod-borne viruses. Dengue virus 1 (Genus Orthoflavivirus) was isolated (isolate no. SA397) from the serum of the 45-year-old female via intracerebral injection in neonatal mice and subsequent passage in VeroE6 cells. Phylogenetic analysis of this strain indicated close genetic identity with cosmopolitan genotype 1 DENV1 strains from Southeast Asia, assigned to major lineage K, minor lineage 1 (DENV1I_K.1), such as GZ8H (99.92%) collected in November 2018 from China, and DV1I-TM19-74 isolate (99.72%) identified in Bangkok, Thailand, in 2019. Serum samples from the 46-year-old male yielded a virus isolate that could not be confirmed as DENV1, prompting unbiased metagenomic sequencing for virus identification and characterization. Illumina sequencing identified multiple segments of a mammalian orthoreovirus (MRV), designated as Human/SA395/SA/2017. Genomic and phylogenetic analyses classified Human/SA395/SA/2017 as MRV-3 and assigned a tentative genotype, MRV-3d, based on the S1 segment. Genomic analyses suggested that Human/SA395/SA/2017 may have originated from reassortments of segments among swine, bat, and human MRVs. The closest identity of the viral attachment protein σ1 (S1) was related to a human isolate identified from Tahiti, French Polynesia, in 1960. This indicates ongoing circulation and co-circulation of Southeast Asian and Polynesian strains, but detailed knowledge is hampered by the limited availability of genomic surveillance. This case represents the rare concurrent detection of two distinct viruses with different transmission routes in the same family with similar clinical presentations. It highlights the complexity of diagnosing diseases with similar sequelae in travelers returning from tropical areas.
{"title":"Detection of Dengue Virus 1 and Mammalian Orthoreovirus 3, with Novel Reassortments, in a South African Family Returning from Thailand, 2017","authors":"Petrus Jansen van Vuren, Rhys H. Parry, J. T. Pawęska","doi":"10.3390/v16081274","DOIUrl":"https://doi.org/10.3390/v16081274","url":null,"abstract":"In July 2017, a family of three members, a 46-year-old male, a 45-year-old female and their 8-year-old daughter, returned to South Africa from Thailand. They presented symptoms consistent with mosquito-borne diseases, including fever, headache, severe body aches and nausea. Mosquito bites in all family members suggested recent exposure to arthropod-borne viruses. Dengue virus 1 (Genus Orthoflavivirus) was isolated (isolate no. SA397) from the serum of the 45-year-old female via intracerebral injection in neonatal mice and subsequent passage in VeroE6 cells. Phylogenetic analysis of this strain indicated close genetic identity with cosmopolitan genotype 1 DENV1 strains from Southeast Asia, assigned to major lineage K, minor lineage 1 (DENV1I_K.1), such as GZ8H (99.92%) collected in November 2018 from China, and DV1I-TM19-74 isolate (99.72%) identified in Bangkok, Thailand, in 2019. Serum samples from the 46-year-old male yielded a virus isolate that could not be confirmed as DENV1, prompting unbiased metagenomic sequencing for virus identification and characterization. Illumina sequencing identified multiple segments of a mammalian orthoreovirus (MRV), designated as Human/SA395/SA/2017. Genomic and phylogenetic analyses classified Human/SA395/SA/2017 as MRV-3 and assigned a tentative genotype, MRV-3d, based on the S1 segment. Genomic analyses suggested that Human/SA395/SA/2017 may have originated from reassortments of segments among swine, bat, and human MRVs. The closest identity of the viral attachment protein σ1 (S1) was related to a human isolate identified from Tahiti, French Polynesia, in 1960. This indicates ongoing circulation and co-circulation of Southeast Asian and Polynesian strains, but detailed knowledge is hampered by the limited availability of genomic surveillance. This case represents the rare concurrent detection of two distinct viruses with different transmission routes in the same family with similar clinical presentations. It highlights the complexity of diagnosing diseases with similar sequelae in travelers returning from tropical areas.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141923181","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}
Luke Heil, Samantha Jewell, J. Lines, Beth A. Garvy
Neonates are more susceptible to influenza virus infection than adults, resulting in increased morbidity and mortality and delayed clearance of the virus. Generating effective CD8+ T cell responses may be important for improving vaccination outcomes in vulnerable populations, but neonatal T cells frequently respond differently than adult cells. We sought to understand CD8+ T cell specificity and immunodominance during neonatal influenza infection and how any differences from the adult hierarchy might impact peptide vaccine effectiveness. Neonatal C57BL/6 mice displayed an altered CD8+ T cell immunodominance hierarchy during influenza infection, preferentially responding to an epitope in the influenza protein PA rather than the co-dominant adult response to NP and PA. Heterosubtypic infections in mice first infected as pups also displayed altered immunodominance and reduced protection compared to mice first infected as adults. Adoptive transfer of influenza-infected bone-marrow-derived dendritic cells promoted an NP-specific CD8+ T cell response in influenza-virus-infected pups and increased viral clearance. Finally, pups responded to PA (224–233), but not NP (366–374) during peptide vaccination. PA (224–233)-vaccinated mice were not protected during viral challenge. Epitope usage should be considered when designing vaccines that target T cells when the intended patient population includes infants and adults.
与成人相比，新生儿更容易感染流感病毒，导致发病率和死亡率增加，病毒清除延迟。产生有效的 CD8+ T 细胞反应对于改善易感人群的疫苗接种效果可能很重要，但新生儿 T 细胞的反应往往与成人细胞不同。我们试图了解新生儿感染流感期间 CD8+ T 细胞的特异性和免疫优势，以及与成人层次结构的差异会如何影响多肽疫苗的效果。新生 C57BL/6 小鼠在流感感染期间显示出改变的 CD8+ T 细胞免疫优势等级，优先对流感蛋白 PA 中的一个表位做出反应，而不是成人对 NP 和 PA 的共同优势反应。与成年小鼠首次感染相比，幼鼠首次感染时的异亚型感染也显示出免疫优势的改变和保护能力的降低。通过收养性转移感染流感的骨髓树突状细胞，促进了感染流感病毒的幼鼠对NP特异性CD8+ T细胞的反应，并提高了病毒清除率。最后，在多肽疫苗接种过程中，幼崽对 PA（224-233）有反应，而对 NP（366-374）没有反应。接种过 PA (224-233) 疫苗的小鼠在病毒挑战中没有保护作用。在设计靶向 T 细胞的疫苗时，如果目标患者群体包括婴儿和成人，则应考虑表位的使用。
{"title":"The Altered Neonatal CD8+ T Cell Immunodominance Hierarchy during Influenza Virus Infection Impacts Peptide Vaccination","authors":"Luke Heil, Samantha Jewell, J. Lines, Beth A. Garvy","doi":"10.3390/v16081271","DOIUrl":"https://doi.org/10.3390/v16081271","url":null,"abstract":"Neonates are more susceptible to influenza virus infection than adults, resulting in increased morbidity and mortality and delayed clearance of the virus. Generating effective CD8+ T cell responses may be important for improving vaccination outcomes in vulnerable populations, but neonatal T cells frequently respond differently than adult cells. We sought to understand CD8+ T cell specificity and immunodominance during neonatal influenza infection and how any differences from the adult hierarchy might impact peptide vaccine effectiveness. Neonatal C57BL/6 mice displayed an altered CD8+ T cell immunodominance hierarchy during influenza infection, preferentially responding to an epitope in the influenza protein PA rather than the co-dominant adult response to NP and PA. Heterosubtypic infections in mice first infected as pups also displayed altered immunodominance and reduced protection compared to mice first infected as adults. Adoptive transfer of influenza-infected bone-marrow-derived dendritic cells promoted an NP-specific CD8+ T cell response in influenza-virus-infected pups and increased viral clearance. Finally, pups responded to PA (224–233), but not NP (366–374) during peptide vaccination. PA (224–233)-vaccinated mice were not protected during viral challenge. Epitope usage should be considered when designing vaccines that target T cells when the intended patient population includes infants and adults.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141923766","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}
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