Deep mutational scanning experiments aid in the surveillance and forecasting of viral evolution by providing prospective measurements of mutational effects on viral traits, but epistatic shifts in the impacts of mutations can hinder viral forecasting when measurements were made in outdated strain backgrounds. Here, we report measurements of the impact of all single amino acid mutations on ACE2-binding affinity and protein folding and expression in the SARS-CoV-2 Omicron BA.2.86 spike receptor-binding domain (RBD). As with other SARS-CoV-2 variants, we find a plastic and evolvable basis for receptor binding, with many mutations at the ACE2 interface maintaining or even improving ACE2-binding affinity. Despite its large genetic divergence, mutational effects in BA.2.86 have not diverged greatly from those measured in its Omicron BA.2 ancestor. However, we do identify strong positive epistasis among subsequent mutations that have accrued in BA.2.86 descendants. Specifically, the Q493E mutation that decreased ACE2-binding affinity in all previous SARS-CoV-2 backgrounds is reversed in sign to enhance human ACE2-binding affinity when coupled with L455S and F456L in the currently emerging KP.3 variant. Our results point to a modest degree of epistatic drift in mutational effects during recent SARS-CoV-2 evolution but highlight how these small epistatic shifts can have important consequences for the emergence of new SARS-CoV-2 variants.
{"title":"Deep mutational scanning of SARS-CoV-2 Omicron BA.2.86 and epistatic emergence of the KP.3 variant","authors":"Ashley L Taylor, Tyler N Starr","doi":"10.1093/ve/veae067","DOIUrl":"https://doi.org/10.1093/ve/veae067","url":null,"abstract":"Deep mutational scanning experiments aid in the surveillance and forecasting of viral evolution by providing prospective measurements of mutational effects on viral traits, but epistatic shifts in the impacts of mutations can hinder viral forecasting when measurements were made in outdated strain backgrounds. Here, we report measurements of the impact of all single amino acid mutations on ACE2-binding affinity and protein folding and expression in the SARS-CoV-2 Omicron BA.2.86 spike receptor-binding domain (RBD). As with other SARS-CoV-2 variants, we find a plastic and evolvable basis for receptor binding, with many mutations at the ACE2 interface maintaining or even improving ACE2-binding affinity. Despite its large genetic divergence, mutational effects in BA.2.86 have not diverged greatly from those measured in its Omicron BA.2 ancestor. However, we do identify strong positive epistasis among subsequent mutations that have accrued in BA.2.86 descendants. Specifically, the Q493E mutation that decreased ACE2-binding affinity in all previous SARS-CoV-2 backgrounds is reversed in sign to enhance human ACE2-binding affinity when coupled with L455S and F456L in the currently emerging KP.3 variant. Our results point to a modest degree of epistatic drift in mutational effects during recent SARS-CoV-2 evolution but highlight how these small epistatic shifts can have important consequences for the emergence of new SARS-CoV-2 variants.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"287 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bethany L Dearlove, Anthony C Fries, Nusrat J Epsi, Stephanie A Richard, Anuradha Ganesan, Nikhil Huprikar, David A Lindholm, Katrin Mende, Rhonda E Colombo, Christopher Colombo, Hongjun Bai, Derek T Larson, Evan C Ewers, Tahaniyat Lalani, Alfred G Smith, Catherine M Berjohn, Ryan C Maves, Milissa U Jones, David Saunders, Carlos J Maldonado, Rupal M Mody, Samantha E Bazan, David R Tribble, Timothy Burgess, Mark P Simons, Brian K Agan, Simon D Pollett, Morgane Rolland
Background COVID-19 vaccine breakthrough infections have been important for all circulating SARS-CoV-2 variant periods, but the contribution of vaccine specific SARS-CoV-2 viral diversification to vaccine failure remains unclear. Methods This study analysed 595 SARS-CoV-2 sequences collected from Military Health System beneficiaries between December 2020 and April 2022 to investigate the impact of vaccination on viral diversity. Results By comparing sequences based on the vaccination status of the participant, we found limited evidence indicating that vaccination was associated with increased viral diversity in the SARS-CoV-2 spike, and we show little to no evidence of a substantial sieve effect within major variants; rather we show that rapid variant replacement constrained intra-genotype COVID-19 vaccine strain immune escape. Conclusions These data suggest that, during past and perhaps future periods of rapid SARS-CoV-2 variant replacement, vaccine-mediated effects were subsumed with other drivers of viral diversity due to the massive scale of infections and vaccinations that occurred in a short time frame. However, our results also highlight some limitations of using sieve analysis methods outside of placebo-controlled clinical trials.
{"title":"SARS-CoV-2 Variant Replacement Constrains Vaccine-Specific Viral Diversification","authors":"Bethany L Dearlove, Anthony C Fries, Nusrat J Epsi, Stephanie A Richard, Anuradha Ganesan, Nikhil Huprikar, David A Lindholm, Katrin Mende, Rhonda E Colombo, Christopher Colombo, Hongjun Bai, Derek T Larson, Evan C Ewers, Tahaniyat Lalani, Alfred G Smith, Catherine M Berjohn, Ryan C Maves, Milissa U Jones, David Saunders, Carlos J Maldonado, Rupal M Mody, Samantha E Bazan, David R Tribble, Timothy Burgess, Mark P Simons, Brian K Agan, Simon D Pollett, Morgane Rolland","doi":"10.1093/ve/veae071","DOIUrl":"https://doi.org/10.1093/ve/veae071","url":null,"abstract":"Background COVID-19 vaccine breakthrough infections have been important for all circulating SARS-CoV-2 variant periods, but the contribution of vaccine specific SARS-CoV-2 viral diversification to vaccine failure remains unclear. Methods This study analysed 595 SARS-CoV-2 sequences collected from Military Health System beneficiaries between December 2020 and April 2022 to investigate the impact of vaccination on viral diversity. Results By comparing sequences based on the vaccination status of the participant, we found limited evidence indicating that vaccination was associated with increased viral diversity in the SARS-CoV-2 spike, and we show little to no evidence of a substantial sieve effect within major variants; rather we show that rapid variant replacement constrained intra-genotype COVID-19 vaccine strain immune escape. Conclusions These data suggest that, during past and perhaps future periods of rapid SARS-CoV-2 variant replacement, vaccine-mediated effects were subsumed with other drivers of viral diversity due to the massive scale of infections and vaccinations that occurred in a short time frame. However, our results also highlight some limitations of using sieve analysis methods outside of placebo-controlled clinical trials.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"69 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Célestin Godwe, Oumarou H Goni, James E San, Nelson Sonela, Mérimé Tchakoute, Aubin Nanfack, Francioli K Koro, Christelle Butel, Nicole Vidal, Ralf Duerr, Darren P Martin, Tulio de Oliveira, Martine Peeters, Marcus Altfeld, Ahidjo Ayouba, Thumbi Ndung’u, Marcel Tongo
From the perspective of developing relevant interventions for treating HIV and controlling its spread, it is particularly important to comprehensively understand the underlying diversity of the virus; especially in countries where the virus has been present and evolving since the cross-species transmission event that triggered the global pandemic. Here we generate and phylogenetically analyse sequences derived from the gag-protease (2010 bp; n=115), partial integrase (345 bp; n=36), and nef (719 bp; n=321) genes of HIV-1 group M (HIV-1M) isolates sampled between 2000 and 2022 from two cosmopolitan cities and 40 remote villages of Cameroon. While 52.4% of all sequenced viruses belonged to circulating recombinant form 02_AG (CRF02_AG), the remainder were highly diverse, collectively representing seven subtypes and sub-subtypes, eight circulating recombinant forms (CRFs), and 36 highly divergent lineages that fall outside the established HIV-1M classification. Additionally, in 77 samples for which at least two genes were typed, 31% of the studied viruses apparently had fragments from viruses belonging to different clades. Furthermore, we found that the distribution of HIV-1M populations are similar between different regions of Cameroon. In contrast, HIV-1M demographics in Cameroon differ significantly from those of its neighbouring countries in the Congo basin (CB). In phylogenetic trees, viral sequences cluster according to the countries where they were sampled, suggesting that while there are minimal geographical or social barriers to viral dissemination throughout Cameroon, there is strongly impeded dispersal of HIV-1M lineages between Cameroon and other locations of the CB. This suggests that the apparent stability of highly diverse Cameroonian HIV-1M populations may be attributable to the extensive mixing of human populations within the country and the concomitant trans-national movements of major lineages with very similar degrees of fitness; coupled with the relatively infrequent inter-national transmission of these lineages from neighboring countries in the CB.
{"title":"Phylogenetic evidence of extensive spatial mixing of diverse HIV-1 group M lineages within Cameroon but not between its neighbours","authors":"Célestin Godwe, Oumarou H Goni, James E San, Nelson Sonela, Mérimé Tchakoute, Aubin Nanfack, Francioli K Koro, Christelle Butel, Nicole Vidal, Ralf Duerr, Darren P Martin, Tulio de Oliveira, Martine Peeters, Marcus Altfeld, Ahidjo Ayouba, Thumbi Ndung’u, Marcel Tongo","doi":"10.1093/ve/veae070","DOIUrl":"https://doi.org/10.1093/ve/veae070","url":null,"abstract":"From the perspective of developing relevant interventions for treating HIV and controlling its spread, it is particularly important to comprehensively understand the underlying diversity of the virus; especially in countries where the virus has been present and evolving since the cross-species transmission event that triggered the global pandemic. Here we generate and phylogenetically analyse sequences derived from the gag-protease (2010 bp; n=115), partial integrase (345 bp; n=36), and nef (719 bp; n=321) genes of HIV-1 group M (HIV-1M) isolates sampled between 2000 and 2022 from two cosmopolitan cities and 40 remote villages of Cameroon. While 52.4% of all sequenced viruses belonged to circulating recombinant form 02_AG (CRF02_AG), the remainder were highly diverse, collectively representing seven subtypes and sub-subtypes, eight circulating recombinant forms (CRFs), and 36 highly divergent lineages that fall outside the established HIV-1M classification. Additionally, in 77 samples for which at least two genes were typed, 31% of the studied viruses apparently had fragments from viruses belonging to different clades. Furthermore, we found that the distribution of HIV-1M populations are similar between different regions of Cameroon. In contrast, HIV-1M demographics in Cameroon differ significantly from those of its neighbouring countries in the Congo basin (CB). In phylogenetic trees, viral sequences cluster according to the countries where they were sampled, suggesting that while there are minimal geographical or social barriers to viral dissemination throughout Cameroon, there is strongly impeded dispersal of HIV-1M lineages between Cameroon and other locations of the CB. This suggests that the apparent stability of highly diverse Cameroonian HIV-1M populations may be attributable to the extensive mixing of human populations within the country and the concomitant trans-national movements of major lineages with very similar degrees of fitness; coupled with the relatively infrequent inter-national transmission of these lineages from neighboring countries in the CB.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"20 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Martínez, Marcela Gómez, Carolina Hernández, Sandra Campo-Palacio, Marina González-Robayo, Marcela Montilla, Norma Pavas-Escobar, Catalina Tovar-Acero, Lillys Geovo-Arias, Esilda Valencia-Urrutia, Nayade Córdoba-Renteria, Marlen Y Carrillo-Hernandez, Julian Ruiz-Saenz, Marlen Martinez-Gutierrez, Alberto Paniz-Mondolfi, Luz H Patiño, Marina Muñoz, Juan David Ramírez
Dengue fever remains as a public health challenge in Colombia, standing as the most prevalent infectious disease in the country. The cyclic nature of dengue epidemics, occurring approximately every three years, is intricately linked to meteorological events like El Niño Southern Oscillation (ENSO). Therefore, the Colombian system faces challenges in genomic surveillance. This study aimed to evaluate local dengue virus (DENV) transmission and genetic diversity in four Colombian departments with heterogeneous incidence patterns (Department is first level territorial units in Colombia). For this study, we processed 26t6 serum samples to identify DENV. Subsequently, we obtained 118 genome sequences by sequencing DENV genomes from serum samples of 134 patients infected with DENV-1 and DENV-2 serotypes. The predominant serotype was DENV-2 (108/143), with the Asian-American (AA) genotype (91/118) being the most prevalent one. Phylogenetic analysis revealed concurrent circulation of two lineages of both DENV-2 AA and DENV-1 V, suggesting ongoing genetic exchange with sequences from Venezuela and Cuba. The continuous migration of Venezuelan citizens into Colombia can contribute to this exchange, emphasizing the need for strengthened prevention measures in border areas. Notably, the Time to Most Recent Common Ancestor analysis identified cryptic transmission of DENV-2 AA since approximately 2015, leading to the recent epidemic. This challenges the notion that major outbreaks are solely triggered by recent virus introductions, emphasizing the importance of active genomic surveillance. The study also highlighted the contrasting selection pressures on DENV-1 V and DENV-2 AA, with the latter experiencing positive selection, possibly influencing its transmissibility. The presence of a cosmopolitan genotype in Colombia, previously reported in Brazil and Peru, raises concerns about transmission routes, emphasizing the necessity for thorough DENV evolution studies. Despite limitations, the study underscores genomic epidemiology’s crucial role in early detection and comprehension of DENV genotypes, recommending the use of advanced sequencing techniques as an early warning system to help prevent and control dengue outbreaks in Colombia and worldwide.
登革热仍然是哥伦比亚的一项公共卫生挑战,是该国最流行的传染病。登革热流行的周期性(大约每三年发生一次)与厄尔尼诺南方涛动(ENSO)等气象事件密切相关。因此,哥伦比亚的基因组监测系统面临着挑战。本研究旨在评估登革热病毒(DENV)在哥伦比亚四个具有不同发病模式的省(省是哥伦比亚的一级领土单位)的传播情况和遗传多样性。在这项研究中,我们处理了 26t6 份血清样本以鉴定 DENV。随后,我们对134名感染DENV-1和DENV-2血清型的患者血清样本中的DENV基因组进行测序,获得了118个基因组序列。最主要的血清型是 DENV-2(108/143),其中亚裔美国人(AA)基因型(91/118)最为流行。系统发生学分析表明,DENV-2 AA 和 DENV-1 V 的两个系同时存在,这表明与委内瑞拉和古巴的序列正在进行遗传交流。委内瑞拉公民向哥伦比亚的持续迁移可能会促成这种交换,这强调了在边境地区加强预防措施的必要性。值得注意的是,"最近共同祖先时间 "分析发现,DENV-2 AA 的隐性传播大约始于 2015 年,导致了最近的疫情。这挑战了重大疫情仅由近期病毒引入引发的观点,强调了积极开展基因组监测的重要性。研究还强调了DENV-1 V和DENV-2 AA的选择压力对比,后者经历了正选择,可能影响了其传播性。哥伦比亚出现了一种世界性的基因型,而此前在巴西和秘鲁也有报道,这引起了人们对传播途径的担忧,强调了对 DENV 演化进行深入研究的必要性。尽管存在局限性,但这项研究强调了基因组流行病学在早期检测和理解 DENV 基因型方面的关键作用,建议使用先进的测序技术作为早期预警系统,帮助预防和控制登革热在哥伦比亚和全球的爆发。
{"title":"Cryptic transmission and novel introduction of Dengue 1 and 2 genotypes in Colombia","authors":"David Martínez, Marcela Gómez, Carolina Hernández, Sandra Campo-Palacio, Marina González-Robayo, Marcela Montilla, Norma Pavas-Escobar, Catalina Tovar-Acero, Lillys Geovo-Arias, Esilda Valencia-Urrutia, Nayade Córdoba-Renteria, Marlen Y Carrillo-Hernandez, Julian Ruiz-Saenz, Marlen Martinez-Gutierrez, Alberto Paniz-Mondolfi, Luz H Patiño, Marina Muñoz, Juan David Ramírez","doi":"10.1093/ve/veae068","DOIUrl":"https://doi.org/10.1093/ve/veae068","url":null,"abstract":"Dengue fever remains as a public health challenge in Colombia, standing as the most prevalent infectious disease in the country. The cyclic nature of dengue epidemics, occurring approximately every three years, is intricately linked to meteorological events like El Niño Southern Oscillation (ENSO). Therefore, the Colombian system faces challenges in genomic surveillance. This study aimed to evaluate local dengue virus (DENV) transmission and genetic diversity in four Colombian departments with heterogeneous incidence patterns (Department is first level territorial units in Colombia). For this study, we processed 26t6 serum samples to identify DENV. Subsequently, we obtained 118 genome sequences by sequencing DENV genomes from serum samples of 134 patients infected with DENV-1 and DENV-2 serotypes. The predominant serotype was DENV-2 (108/143), with the Asian-American (AA) genotype (91/118) being the most prevalent one. Phylogenetic analysis revealed concurrent circulation of two lineages of both DENV-2 AA and DENV-1 V, suggesting ongoing genetic exchange with sequences from Venezuela and Cuba. The continuous migration of Venezuelan citizens into Colombia can contribute to this exchange, emphasizing the need for strengthened prevention measures in border areas. Notably, the Time to Most Recent Common Ancestor analysis identified cryptic transmission of DENV-2 AA since approximately 2015, leading to the recent epidemic. This challenges the notion that major outbreaks are solely triggered by recent virus introductions, emphasizing the importance of active genomic surveillance. The study also highlighted the contrasting selection pressures on DENV-1 V and DENV-2 AA, with the latter experiencing positive selection, possibly influencing its transmissibility. The presence of a cosmopolitan genotype in Colombia, previously reported in Brazil and Peru, raises concerns about transmission routes, emphasizing the necessity for thorough DENV evolution studies. Despite limitations, the study underscores genomic epidemiology’s crucial role in early detection and comprehension of DENV genotypes, recommending the use of advanced sequencing techniques as an early warning system to help prevent and control dengue outbreaks in Colombia and worldwide.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"54 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Majdouline El Moussaoui, Sebastien Bontems, Cecile Meex, Marie-Pierre Hayette, Marie Lejeune, Samuel L Hong, Simon Dellicour, Michel Moutschen, Nadine Cambisano, Nathalie Renotte, Vincent Bours, Gilles Darcis, Maria Artesi, Keith Durkin
Accumulating evidence points to persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunocompromised individuals as a source of novel lineages. While intrahost evolution of the virus in chronically infected patients has previously been reported, existing knowledge is primarily based on samples from the nasopharynx. In this study, we investigate the intrahost evolution and genetic diversity that accumulated during a prolonged SARS-CoV-2 infection with the Omicron sublineage BF.7, estimated to have persisted for over one year in an immunosuppressed patient. Based on the sequencing of eight samples collected at six time points, we identified 87 intrahost single-nucleotide variants (iSNVs), two indels, and a 362 bp deletion. Our analysis revealed distinct viral genotypes in the nasopharyngeal (NP), endotracheal aspirate (ETA), and bronchoalveolar (BAL) samples. This suggests that NP samples may not offer a comprehensive representation of the overall intrahost viral diversity. Our findings not only demonstrate that the Omicron sublineage BF.7 can further diverge from its already exceptionally mutated state but also highlight that patients chronically infected with SARS-CoV-2 can develop genetically specific viral populations across distinct anatomical compartments. This provides novel insights into the intricate nature of viral diversity and evolution dynamics in persistent infections.
{"title":"Intrahost evolution leading to distinct lineages in the upper and lower respiratory tracts during SARS-CoV-2 prolonged infection","authors":"Majdouline El Moussaoui, Sebastien Bontems, Cecile Meex, Marie-Pierre Hayette, Marie Lejeune, Samuel L Hong, Simon Dellicour, Michel Moutschen, Nadine Cambisano, Nathalie Renotte, Vincent Bours, Gilles Darcis, Maria Artesi, Keith Durkin","doi":"10.1093/ve/veae073","DOIUrl":"https://doi.org/10.1093/ve/veae073","url":null,"abstract":"Accumulating evidence points to persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunocompromised individuals as a source of novel lineages. While intrahost evolution of the virus in chronically infected patients has previously been reported, existing knowledge is primarily based on samples from the nasopharynx. In this study, we investigate the intrahost evolution and genetic diversity that accumulated during a prolonged SARS-CoV-2 infection with the Omicron sublineage BF.7, estimated to have persisted for over one year in an immunosuppressed patient. Based on the sequencing of eight samples collected at six time points, we identified 87 intrahost single-nucleotide variants (iSNVs), two indels, and a 362 bp deletion. Our analysis revealed distinct viral genotypes in the nasopharyngeal (NP), endotracheal aspirate (ETA), and bronchoalveolar (BAL) samples. This suggests that NP samples may not offer a comprehensive representation of the overall intrahost viral diversity. Our findings not only demonstrate that the Omicron sublineage BF.7 can further diverge from its already exceptionally mutated state but also highlight that patients chronically infected with SARS-CoV-2 can develop genetically specific viral populations across distinct anatomical compartments. This provides novel insights into the intricate nature of viral diversity and evolution dynamics in persistent infections.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"4 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seungwon Kim, Godfrey Kigozi, Michael A Martin, Ronald M Galiwango, Thomas C Quinn, Andrew D Redd, Robert Ssekubugu, David Bonsall, Deogratius Ssemwanga, Andrew Rambaut, Joshua T Herbeck, Steven J Reynolds, Brian Foley, Lucie Abeler-Dörner, Christophe Fraser, Oliver Ratmann, Joseph Kagaayi, Oliver Laeyendecker, M Kate Grabowski
There is limited data on HIV evolutionary trends in African populations. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a twenty-four-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. Gag (p24) and env (gp41) HIV data were generated from persons living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994 to 2018) and four hyperendemic Lake Victoria fishing communities (2011 to 2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was evaluated using the Shannon diversity index and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Demographic history of HIV was inferred using a coalescent-based Bayesian Skygrid model. Evolutionary dynamics were assessed among demographic and behavioral population sub-groups, including by migration status. 9,931 HIV sequences were available from 4,999 PLHIV, including 3,060 and 1,939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 (p<0.001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 (p<0.001). The proportion of viruses classified as recombinants significantly increased by nearly four-fold from 12.2% in 1995 to 44.8% in 2017. Inter-subtype HIV diversity has generally increased. While intra-subtype p24 genetic diversity and divergence leveled off after 2014, intra-subtype gp41 diversity, effective population size, and divergence increased through 2017. Intra- and inter-subtype viral diversity increased across all demographic and behavioral population sub-groups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development.
有关非洲人群中 HIV 演变趋势的数据十分有限。我们利用拉卡伊社区队列研究(Rakai Community Cohort Study)的 HIV 序列和调查数据,评估了乌干达南部地区 HIV 病毒多样性和基因分化的变化,该研究跨越了 HIV 预防和治疗项目的引入和扩大的二十四年。Gag (p24) 和 env (gp41) HIV 数据来自 31 个内陆半城市贸易和农业社区(1994 年至 2018 年)和 4 个维多利亚湖高流行性渔业社区(2011 年至 2018 年)的艾滋病毒感染者。艾滋病毒亚型是通过系统发生学确认的重组鉴定程序确定的。亚型间多样性采用香农多样性指数进行评估,亚型内多样性采用核苷酸多样性和成对 TN93 遗传距离进行评估。利用根尖距离和成对 TN93 遗传距离分析测量遗传差异。使用基于聚合的贝叶斯 Skygrid 模型推断了 HIV 的流行历史。评估了人口和行为亚群之间的进化动态,包括迁移状况。从 4999 名艾滋病毒感染者中获得了 9931 个艾滋病毒序列,其中包括分别居住在内陆和渔业社区的 3060 人和 1939 人。在内陆社区,A1亚型病毒的比例从1995年的14.3%上升到2017年的25.9%(p<0.001),而D亚型病毒的比例从1995年的73.2%下降到2017年的28.2%(p<0.001)。被归类为重组病毒的比例从 1995 年的 12.2% 大幅增至 2017 年的 44.8%,增长了近四倍。艾滋病毒亚型间的多样性普遍增加。2014 年后,亚型内 p24 遗传多样性和分化趋于平稳,而亚型内 gp41 多样性、有效种群规模和分化则在 2017 年有所增加。亚型内和亚型间病毒多样性在所有人口和行为人群亚群中都有所增加,包括近期无迁徙史或无社区外性伴侣的人群。这项研究为我们提供了有关艾滋病防治计划扩大后人群层面艾滋病病毒演变动态的见解。持续的分子监测可使人们更好地了解驱动人群艾滋病病毒进化的动态,并为疫情控制和疫苗开发提供重要启示。
{"title":"Intra- and inter-subtype HIV diversity between 1994 and 2018 in southern Uganda: a longitudinal population-based study","authors":"Seungwon Kim, Godfrey Kigozi, Michael A Martin, Ronald M Galiwango, Thomas C Quinn, Andrew D Redd, Robert Ssekubugu, David Bonsall, Deogratius Ssemwanga, Andrew Rambaut, Joshua T Herbeck, Steven J Reynolds, Brian Foley, Lucie Abeler-Dörner, Christophe Fraser, Oliver Ratmann, Joseph Kagaayi, Oliver Laeyendecker, M Kate Grabowski","doi":"10.1093/ve/veae065","DOIUrl":"https://doi.org/10.1093/ve/veae065","url":null,"abstract":"There is limited data on HIV evolutionary trends in African populations. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a twenty-four-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. Gag (p24) and env (gp41) HIV data were generated from persons living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994 to 2018) and four hyperendemic Lake Victoria fishing communities (2011 to 2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was evaluated using the Shannon diversity index and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Demographic history of HIV was inferred using a coalescent-based Bayesian Skygrid model. Evolutionary dynamics were assessed among demographic and behavioral population sub-groups, including by migration status. 9,931 HIV sequences were available from 4,999 PLHIV, including 3,060 and 1,939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 (p&lt;0.001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 (p&lt;0.001). The proportion of viruses classified as recombinants significantly increased by nearly four-fold from 12.2% in 1995 to 44.8% in 2017. Inter-subtype HIV diversity has generally increased. While intra-subtype p24 genetic diversity and divergence leveled off after 2014, intra-subtype gp41 diversity, effective population size, and divergence increased through 2017. Intra- and inter-subtype viral diversity increased across all demographic and behavioral population sub-groups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"8 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ulad Litvin, Eddie C.Y Wang, Richard J Stanton, Ceri A Fielding, Joseph Hughes
Cytomegalovirus is a genus of herpesviruses, members of which share a long history of co-evolution with their primate hosts including Great Apes, Old and New World monkeys. These viruses are ubiquitous within their host populations and establish lifelong infection in most individuals. Although asymptomatic in healthy individuals, infection poses a significant risk to individuals with a weakened or underdeveloped immune system. The genome of human cytomegalovirus is the largest among human-infecting viruses, and comprises at least fifteen separate gene families, which may have arisen by gene duplication. Within human cytomegalovirus, the RL11 gene family is the largest. RL11 genes are non-essential in vitro but have immune evasion roles that are likely critical to persistence in vivo. These genes demonstrate an extreme level of inter-species and intra-strain sequence diversity, that makes it challenging to deduce the evolutionary relationships within this gene family. Understanding the evolutionary relationships of these genes, especially accurate ortholog identification, is essential for reconstructing ancestral genomes, deciphering gene repertoire and order, and enabling reliable functional analyses across the Cytomegalovirus species, thereby offering insights into evolutionary processes, genetic diversity, and the functional significance of genes. In this work, we combined in silico genome screening with sequence-based and structure-guided phylogenetic analysis to reconstruct the evolutionary history of the RL11 gene family. We confirmed that RL11 genes are unique to cytomegaloviruses of Old World monkeys and Great Apes, showing that this gene family was formed by multiple early duplication events and later lineage-specific losses. We identified four main clades of RL11 genes and showed that their expansions were mainly lineage-specific and happened independently in cytomegaloviruses of Great Apes, African Old World monkeys and Asian Old World monkeys. We also identified groups of orthologous genes across the Cytomegalovirus tree showing that some human cytomegalovirus-specific RL11 genes emerged before the divergence of human and chimpanzee cytomegaloviruses but were subsequently lost in the latter. The extensive and dynamic species-specific evolution of this gene family suggests their functions target elements of host immunity that have similarly co-evolved during speciation.
{"title":"Evolution of the Cytomegalovirus RL11 Gene Family in Old World monkeys and Great Apes","authors":"Ulad Litvin, Eddie C.Y Wang, Richard J Stanton, Ceri A Fielding, Joseph Hughes","doi":"10.1093/ve/veae066","DOIUrl":"https://doi.org/10.1093/ve/veae066","url":null,"abstract":"Cytomegalovirus is a genus of herpesviruses, members of which share a long history of co-evolution with their primate hosts including Great Apes, Old and New World monkeys. These viruses are ubiquitous within their host populations and establish lifelong infection in most individuals. Although asymptomatic in healthy individuals, infection poses a significant risk to individuals with a weakened or underdeveloped immune system. The genome of human cytomegalovirus is the largest among human-infecting viruses, and comprises at least fifteen separate gene families, which may have arisen by gene duplication. Within human cytomegalovirus, the RL11 gene family is the largest. RL11 genes are non-essential in vitro but have immune evasion roles that are likely critical to persistence in vivo. These genes demonstrate an extreme level of inter-species and intra-strain sequence diversity, that makes it challenging to deduce the evolutionary relationships within this gene family. Understanding the evolutionary relationships of these genes, especially accurate ortholog identification, is essential for reconstructing ancestral genomes, deciphering gene repertoire and order, and enabling reliable functional analyses across the Cytomegalovirus species, thereby offering insights into evolutionary processes, genetic diversity, and the functional significance of genes. In this work, we combined in silico genome screening with sequence-based and structure-guided phylogenetic analysis to reconstruct the evolutionary history of the RL11 gene family. We confirmed that RL11 genes are unique to cytomegaloviruses of Old World monkeys and Great Apes, showing that this gene family was formed by multiple early duplication events and later lineage-specific losses. We identified four main clades of RL11 genes and showed that their expansions were mainly lineage-specific and happened independently in cytomegaloviruses of Great Apes, African Old World monkeys and Asian Old World monkeys. We also identified groups of orthologous genes across the Cytomegalovirus tree showing that some human cytomegalovirus-specific RL11 genes emerged before the divergence of human and chimpanzee cytomegaloviruses but were subsequently lost in the latter. The extensive and dynamic species-specific evolution of this gene family suggests their functions target elements of host immunity that have similarly co-evolved during speciation.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"29 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22eCollection Date: 2024-01-01DOI: 10.1093/ve/veae062
Chenxi Li, Yazhou Hu, Yuhang Liu, Nan Li, Le Yi, Changchun Tu, Biao He
Amphibians are an essential class in the maintenance of global ecosystem equilibrium, but they face serious extinction risks driven by climate change and infectious diseases. Unfortunately, the virus diversity harbored by these creatures has been rarely investigated. By profiling the virus flora residing in different tissues of 100 farmed black-spotted frogs (Rana nigromaculata) using a combination of DNA and RNA viromic methods, we captured 28 high-quality viral sequences covering at least 11 viral families. Most of these sequences were remarkably divergent, adding at least 10 new species and 4 new genera within the families Orthomyxoviridae, Adenoviridae, Nodaviridae, Phenuiviridae, and Picornaviridae. We recovered five orthomyxovirus segments, with three distantly neighboring two Chinese fish-related viruses. The recombination event of frog virus 3 occurred among the frog and turtle strains. The relative abundance and molecular detection revealed different tissue tropisms of these viruses, with the orthomyxovirus and adenoviruses being enteric and probably also neurotropic, but the new astrovirus and picornavirus being hepatophilic. These results expand the spectrum of viruses harbored by anurans, highlighting the necessity to continuously monitor these viruses and to investigate the virus diversity in a broader area with more diverse amphibian species.
{"title":"The tissue virome of black-spotted frogs reveals a diversity of uncharacterized viruses.","authors":"Chenxi Li, Yazhou Hu, Yuhang Liu, Nan Li, Le Yi, Changchun Tu, Biao He","doi":"10.1093/ve/veae062","DOIUrl":"10.1093/ve/veae062","url":null,"abstract":"<p><p>Amphibians are an essential class in the maintenance of global ecosystem equilibrium, but they face serious extinction risks driven by climate change and infectious diseases. Unfortunately, the virus diversity harbored by these creatures has been rarely investigated. By profiling the virus flora residing in different tissues of 100 farmed black-spotted frogs (<i>Rana nigromaculata</i>) using a combination of DNA and RNA viromic methods, we captured 28 high-quality viral sequences covering at least 11 viral families. Most of these sequences were remarkably divergent, adding at least 10 new species and 4 new genera within the families <i>Orthomyxoviridae, Adenoviridae, Nodaviridae, Phenuiviridae</i>, and <i>Picornaviridae</i>. We recovered five orthomyxovirus segments, with three distantly neighboring two Chinese fish-related viruses. The recombination event of frog virus 3 occurred among the frog and turtle strains. The relative abundance and molecular detection revealed different tissue tropisms of these viruses, with the orthomyxovirus and adenoviruses being enteric and probably also neurotropic, but the new astrovirus and picornavirus being hepatophilic. These results expand the spectrum of viruses harbored by anurans, highlighting the necessity to continuously monitor these viruses and to investigate the virus diversity in a broader area with more diverse amphibian species.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae062"},"PeriodicalIF":5.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-17eCollection Date: 2024-01-01DOI: 10.1093/ve/veae064
Art F Y Poon
Hemagglutinin (HA) and neuraminidase (NA) proteins are the primary antigenic targets of influenza A virus (IAV) infections. IAV infections are generally classified into subtypes of HA and NA proteins, e.g. H3N2. Most of the known subtypes were originally defined by a lack of antibody cross-reactivity. However, genetic sequencing has played an increasingly important role in characterizing the evolving diversity of IAV. Novel subtypes have recently been described solely by their genetic sequences, and IAV infections are routinely subtyped by molecular assays, or the comparison of sequences to references. In this study, I carry out a comparative analysis of all available IAV protein sequences in the Genbank database (over 1.1 million, reduced to 272,292 unique sequences prior to phylogenetic reconstruction) to determine whether the serologically defined subtypes can be reproduced with sequence-based criteria. I show that a robust genetic taxonomy of HA and NA subtypes can be obtained using a simple clustering method, namely, by progressively partitioning the phylogeny on its longest internal branches. However, this taxonomy also requires some amendments to the current nomenclature. For example, two IAV isolates from bats previously characterized as a divergent lineage of H9N2 should be separated into their own subtype. With the exception of these small and highly divergent lineages, the phylogenies relating each of the other six genomic segments do not support partitions into major subtypes.
血凝素(HA)和神经氨酸酶(NA)蛋白是甲型流感病毒(IAV)感染的主要抗原目标。IAV 感染一般分为 HA 和 NA 蛋白亚型,如 H3N2。大多数已知亚型最初是通过缺乏抗体交叉反应来定义的。然而,基因测序在描述 IAV 不断演变的多样性方面发挥着越来越重要的作用。最近,一些新的亚型仅通过其基因序列就被描述出来,而 IAV 感染通常是通过分子检测或将序列与参考文献进行比较来确定亚型的。在本研究中,我对 Genbank 数据库中所有可用的 IAV 蛋白序列(超过 110 万个,在系统发育重建前已减少到 272 292 个唯一序列)进行了比较分析,以确定血清学定义的亚型是否可以通过基于序列的标准再现。我的研究表明,使用简单的聚类方法,即在最长的内部分支上逐步划分系统发育,就能获得稳健的 HA 和 NA 亚型遗传分类法。不过,这种分类法也需要对目前的命名法进行一些修改。例如,以前被定性为 H9N2 分歧系的两个蝙蝠 IAV 分离物应被分离成各自的亚型。除了这些高度分化的小系外,与其他六个基因组片段相关的系统发育并不支持将其划分为主要亚型。
{"title":"Prospects for a sequence-based taxonomy of influenza A virus subtypes.","authors":"Art F Y Poon","doi":"10.1093/ve/veae064","DOIUrl":"10.1093/ve/veae064","url":null,"abstract":"<p><p>Hemagglutinin (HA) and neuraminidase (NA) proteins are the primary antigenic targets of influenza A virus (IAV) infections. IAV infections are generally classified into subtypes of HA and NA proteins, e.g. H3N2. Most of the known subtypes were originally defined by a lack of antibody cross-reactivity. However, genetic sequencing has played an increasingly important role in characterizing the evolving diversity of IAV. Novel subtypes have recently been described solely by their genetic sequences, and IAV infections are routinely subtyped by molecular assays, or the comparison of sequences to references. In this study, I carry out a comparative analysis of all available IAV protein sequences in the Genbank database (over 1.1 million, reduced to 272,292 unique sequences prior to phylogenetic reconstruction) to determine whether the serologically defined subtypes can be reproduced with sequence-based criteria. I show that a robust genetic taxonomy of HA and NA subtypes can be obtained using a simple clustering method, namely, by progressively partitioning the phylogeny on its longest internal branches. However, this taxonomy also requires some amendments to the current nomenclature. For example, two IAV isolates from bats previously characterized as a divergent lineage of H9N2 should be separated into their own subtype. With the exception of these small and highly divergent lineages, the phylogenies relating each of the other six genomic segments do not support partitions into major subtypes.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae064"},"PeriodicalIF":5.5,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The enigmatic origins and transmission events of the gibbon ape leukemia virus (GALV) and its close relative, the koala retrovirus (KoRV) have been a source of enduring debate. Bats and rodents are each proposed as major reservoirs of interspecies transmission, with ongoing efforts to identify additional animal hosts of GALV-KoRV-related retroviruses. In this study, we identified nine rodent species as novel hosts of GALV-KoRV-related retroviruses. Included among these hosts are two African rodents, revealing the first appearance of this clade beyond the Australian and Southeast Asian region. One of these African rodents, Mastomys natalensis, carries an endogenous GALV-KoRV-related retrovirus that is fully intact and potentially still infectious. Our findings support the hypothesis that rodents are the major carriers of GALV-KoRV-related retroviruses.
{"title":"GALV-KoRV-related retroviruses in diverse Australian and African rodent species.","authors":"Joshua A Hayward, Shuoshuo Tian, Gilda Tachedjian","doi":"10.1093/ve/veae061","DOIUrl":"https://doi.org/10.1093/ve/veae061","url":null,"abstract":"The enigmatic origins and transmission events of the gibbon ape leukemia virus (GALV) and its close relative, the koala retrovirus (KoRV) have been a source of enduring debate. Bats and rodents are each proposed as major reservoirs of interspecies transmission, with ongoing efforts to identify additional animal hosts of GALV-KoRV-related retroviruses. In this study, we identified nine rodent species as novel hosts of GALV-KoRV-related retroviruses. Included among these hosts are two African rodents, revealing the first appearance of this clade beyond the Australian and Southeast Asian region. One of these African rodents, Mastomys natalensis, carries an endogenous GALV-KoRV-related retrovirus that is fully intact and potentially still infectious. Our findings support the hypothesis that rodents are the major carriers of GALV-KoRV-related retroviruses.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"16 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}