Alyssa T Pyke, Daniel J Wilson, Alice Michie, John S Mackenzie, Allison Imrie, Jane Cameron, Stephen L Doggett, John Haniotis, Lara J Herrero, Leon Caly, Stacey E Lynch, Peter T Mee, Eugene T Madzokere, Ana L Ramirez, Devina Paramitha, Jody Hobson-Peters, David W Smith, Richard Weir, Mitchell Sullivan, Julian Druce, Lorna Melville, Jennifer Robson, Robert Gibb, Andrew F van den Hurk, Sebastian Duchene
Ross River virus (RRV) and Barmah Forest virus (BFV) are arthritogenic arthropod-borne viruses (arboviruses) that exhibit generalist host associations and share distributions in Australia and Papua New Guinea (PNG). Using stochastic mapping and discrete-trait phylogenetic analyses we profiled the independent evolution of RRV and BFV signature mutations. Analysis of 186 RRV and 88 BFV genomes demonstrated their viral evolution trajectories have involved repeated selection of mutations, particularly in the nonstructural protein 1 (nsP1) and envelope 3 (E3) genes suggesting convergent evolution. Convergent mutations in the nsP1 genes of RRV (residues 248 and 441) and BFV (residues 297 and 447) may be involved with catalytic enzyme mechanisms and host membrane interactions during viral RNA replication and capping. Convergent E3 mutations (RRV site 59 and BFV site 57) may be associated with enzymatic furin activity and cleavage of E3 from protein precursors assisting viral maturation and infectivity. Given their requirement to replicate in disparate insect and vertebrate hosts, convergent evolution in RRV and BFV may represent a dynamic link between their requirement to selectively ‘fine-tune’ intracellular host interactions and viral replicative enzymatic processes. Despite evidence of evolutionary convergence, selection pressure analyses did not reveal any RRV or BFV amino acid sites under strong positive selection and only weak positive selection for nonstructural protein sites. These findings may indicate that their alphavirus ancestors were subject to positive selection events which predisposed ongoing pervasive convergent evolution, and this largely supports continued purifying selection in RRV and BFV populations during their replication in mosquito and vertebrate hosts.
{"title":"Independent repeated mutations within the alphaviruses Ross River virus and Barmah Forest virus indicates convergent evolution and past positive selection in ancestral populations despite ongoing purifying selection","authors":"Alyssa T Pyke, Daniel J Wilson, Alice Michie, John S Mackenzie, Allison Imrie, Jane Cameron, Stephen L Doggett, John Haniotis, Lara J Herrero, Leon Caly, Stacey E Lynch, Peter T Mee, Eugene T Madzokere, Ana L Ramirez, Devina Paramitha, Jody Hobson-Peters, David W Smith, Richard Weir, Mitchell Sullivan, Julian Druce, Lorna Melville, Jennifer Robson, Robert Gibb, Andrew F van den Hurk, Sebastian Duchene","doi":"10.1093/ve/veae080","DOIUrl":"https://doi.org/10.1093/ve/veae080","url":null,"abstract":"Ross River virus (RRV) and Barmah Forest virus (BFV) are arthritogenic arthropod-borne viruses (arboviruses) that exhibit generalist host associations and share distributions in Australia and Papua New Guinea (PNG). Using stochastic mapping and discrete-trait phylogenetic analyses we profiled the independent evolution of RRV and BFV signature mutations. Analysis of 186 RRV and 88 BFV genomes demonstrated their viral evolution trajectories have involved repeated selection of mutations, particularly in the nonstructural protein 1 (nsP1) and envelope 3 (E3) genes suggesting convergent evolution. Convergent mutations in the nsP1 genes of RRV (residues 248 and 441) and BFV (residues 297 and 447) may be involved with catalytic enzyme mechanisms and host membrane interactions during viral RNA replication and capping. Convergent E3 mutations (RRV site 59 and BFV site 57) may be associated with enzymatic furin activity and cleavage of E3 from protein precursors assisting viral maturation and infectivity. Given their requirement to replicate in disparate insect and vertebrate hosts, convergent evolution in RRV and BFV may represent a dynamic link between their requirement to selectively ‘fine-tune’ intracellular host interactions and viral replicative enzymatic processes. Despite evidence of evolutionary convergence, selection pressure analyses did not reveal any RRV or BFV amino acid sites under strong positive selection and only weak positive selection for nonstructural protein sites. These findings may indicate that their alphavirus ancestors were subject to positive selection events which predisposed ongoing pervasive convergent evolution, and this largely supports continued purifying selection in RRV and BFV populations during their replication in mosquito and vertebrate hosts.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"78 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257006","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}
Liuxia Peng, Ziying Jin, Peiwen Chen, Zengfeng Zhang, Xiaohui Fan, Wenshan Hong, Yongmei Liu, David K Smith, William Yiu-Man Cheung, Jia Wang, Huachen Zhu, Tommy Tsan-Yuk Lam, Yi Guan
Geese, both wild and domestic, are generally considered part of the natural reservoir for influenza A viruses. The highly pathogenic H5 Goose/Guangdong avian influenza virus lineage that is still causing outbreaks worldwide was first detected in domestic geese in 1996. However, while wild geese might have a somewhat restricted role in the influenza ecosystem, the role of domestic geese is little studied. Here, 109 H6 viruses isolated from domestic geese during 2001-2018 in southern China had their phylogeny, evolutionary dynamics, and molecular signatures characterized to examine the role of domestic geese. Our findings demonstrated that all geese H6 viruses were derived from H6 viruses established in ducks and that they subsequently formed three distinct hemagglutinin lineages. Rapid evolution of the hemagglutinin genes was not detected after the duck-to-goose transmissions of H6 viruses that then circulated in geese. Despite long-term persistence in geese, H6 viruses were rarely observed to transmit back to ducks or terrestrial poultry and never exchanged genes with viruses from other subtypes. Most geese H6 viruses maintained the primary molecular signatures of their duck precursors. This study raises the possibility that, rather than being part of the natural reservoir, domestic geese might be more like an aberrant host species for influenza A viruses, and perhaps a “dead-end” host.
{"title":"Evolutionary characterization of the establishment of H6 influenza viruses in domestic geese in China: implications for the position of the host in the ecosystem","authors":"Liuxia Peng, Ziying Jin, Peiwen Chen, Zengfeng Zhang, Xiaohui Fan, Wenshan Hong, Yongmei Liu, David K Smith, William Yiu-Man Cheung, Jia Wang, Huachen Zhu, Tommy Tsan-Yuk Lam, Yi Guan","doi":"10.1093/ve/veae075","DOIUrl":"https://doi.org/10.1093/ve/veae075","url":null,"abstract":"Geese, both wild and domestic, are generally considered part of the natural reservoir for influenza A viruses. The highly pathogenic H5 Goose/Guangdong avian influenza virus lineage that is still causing outbreaks worldwide was first detected in domestic geese in 1996. However, while wild geese might have a somewhat restricted role in the influenza ecosystem, the role of domestic geese is little studied. Here, 109 H6 viruses isolated from domestic geese during 2001-2018 in southern China had their phylogeny, evolutionary dynamics, and molecular signatures characterized to examine the role of domestic geese. Our findings demonstrated that all geese H6 viruses were derived from H6 viruses established in ducks and that they subsequently formed three distinct hemagglutinin lineages. Rapid evolution of the hemagglutinin genes was not detected after the duck-to-goose transmissions of H6 viruses that then circulated in geese. Despite long-term persistence in geese, H6 viruses were rarely observed to transmit back to ducks or terrestrial poultry and never exchanged genes with viruses from other subtypes. Most geese H6 viruses maintained the primary molecular signatures of their duck precursors. This study raises the possibility that, rather than being part of the natural reservoir, domestic geese might be more like an aberrant host species for influenza A viruses, and perhaps a “dead-end” host.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"30 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257005","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}
The World Health Organization has set a target to eliminate viral hepatitis as a public threat by 2030. In pursuit of this goal, Thailand initiated a hepatitis C virus (HCV) micro-elimination project targeting Phetchabun province, a well-recognized high-burden HCV endemic area. However, the historical transmission dynamics of HCV in Phetchabun, and in Thailand in general, remain unclear. This study investigates the epidemic histories of HCV in Phetchabun, focusing on subtypes 1b, 3a, and 6f, and their relationship with HCV in other regions of Thailand, using molecular phylogenetic analyses. Our results reveal nationwide presence of subtypes 1b, and 3a, while subtype 6f is mainly confined to Phetchabun. The initial spread of subtype 1b was inferred to coincide with World War II and the period of suboptimal medical and hygienic standards in Thai blood transfusion services, suggesting a correlation between the two. The early expansion of subtype 3a was, on the other hand, found to correlate with the epidemic of intravenous drug use in Thailand during the time of Vietnam War. The early expansion of subtype 6f, in contrast, appears to coincide with the period of severe regional political conflict and social and economic instability. All these findings suggest the complex interplay between social determinants of health and HCV transmission. Post the mid-1990s/early 2000s, all subtypes showed significantly reduced population growth rates, aligning with improvements in blood transfusion safety standards, the nationwide “War on Drugs” policy, and enhanced accessibility to public healthcare and HCV treatments. These combined efforts likely have contributed to curbing the spread of HCV in Thailand. Nevertheless, our analyses reveal that the prevalence of HCV in Thailand remains high overall, emphasizing the need for further research and a nationwide approach to more effectively reduce the HCV burden in Thailand.
{"title":"Historical drivers of HCV subtypes 1b and 3a in Thailand, and 6f in Phetchabun, an HCV endemic area of the country","authors":"Rujipat Wasitthankasem, Pakorn Aiewsakun, Sutthinee Lapchai, Maneerat Raksayot, Chantisa Keeratipusana, Pakawat Jarupund, Vorthunju Nakhonsri, Napaporn Pimsing, Sissades Tongsima, Yong Poovorawan","doi":"10.1093/ve/veae079","DOIUrl":"https://doi.org/10.1093/ve/veae079","url":null,"abstract":"The World Health Organization has set a target to eliminate viral hepatitis as a public threat by 2030. In pursuit of this goal, Thailand initiated a hepatitis C virus (HCV) micro-elimination project targeting Phetchabun province, a well-recognized high-burden HCV endemic area. However, the historical transmission dynamics of HCV in Phetchabun, and in Thailand in general, remain unclear. This study investigates the epidemic histories of HCV in Phetchabun, focusing on subtypes 1b, 3a, and 6f, and their relationship with HCV in other regions of Thailand, using molecular phylogenetic analyses. Our results reveal nationwide presence of subtypes 1b, and 3a, while subtype 6f is mainly confined to Phetchabun. The initial spread of subtype 1b was inferred to coincide with World War II and the period of suboptimal medical and hygienic standards in Thai blood transfusion services, suggesting a correlation between the two. The early expansion of subtype 3a was, on the other hand, found to correlate with the epidemic of intravenous drug use in Thailand during the time of Vietnam War. The early expansion of subtype 6f, in contrast, appears to coincide with the period of severe regional political conflict and social and economic instability. All these findings suggest the complex interplay between social determinants of health and HCV transmission. Post the mid-1990s/early 2000s, all subtypes showed significantly reduced population growth rates, aligning with improvements in blood transfusion safety standards, the nationwide “War on Drugs” policy, and enhanced accessibility to public healthcare and HCV treatments. These combined efforts likely have contributed to curbing the spread of HCV in Thailand. Nevertheless, our analyses reveal that the prevalence of HCV in Thailand remains high overall, emphasizing the need for further research and a nationwide approach to more effectively reduce the HCV burden in Thailand.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"74 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217233","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}
Michelle Wille, Ivano Broz, Tanya Cherrington, Allison Crawley, Blaine Farrugia, Mark Ford, Melinda Frost, Joanne Grimsey, Peter D Kirkland, Shaylie Latimore, Stacey E Lynch, Sue Martin, Cornelius Matereke, Peter T Mee, Matthew J Neave, Mark O’Dea, Andrew J Read, Kim O’Riley, Vittoria Stevens, Sivapiragasam Thayaparan, Sara Zufan, Silvia Ban de Gouvea Pedroso, Victoria Grillo, Andrew C Breed, Ian G Barr, Edward C Holmes, Marcel Klaassen, Frank Y K Wong
The current panzootic of high pathogenicity avian influenza virus H5N1 demonstrates how viral incursions can have major ramifications for wildlife and domestic animals. Herein, we describe the recent incursion into Australia of two low pathogenicity avian influenza virus subtypes, H4 and H10, that exhibited contrasting evolutionary dynamics. Viruses detected from national surveillance and disease investigations between 2020-2022 revealed 27 genomes, 24 of which have at least one segment more closely related to Eurasian or North American avian influenza lineages than those already circulating in Australia. Phylogenetic analysis revealed that H4 viruses circulating in shorebirds represent a recent incursion from Asia that is distinct from those circulating concurrently in Australian waterfowl. Analysis of the internal segments further demonstrates exclusive, persistent circulation in shorebirds. This contrasts with H10, where a novel lineage has emerged in wild waterfowl, poultry and captive birds across Australia, and has likely replaced previously circulating H10 lineages through competitive exclusion. Elucidating different dynamics for avian influenza incursions supports effective disease risk identification and communication that better informs disease preparedness and response.
{"title":"Contrasting dynamics of two incursions of low pathogenicity avian influenza virus into Australia","authors":"Michelle Wille, Ivano Broz, Tanya Cherrington, Allison Crawley, Blaine Farrugia, Mark Ford, Melinda Frost, Joanne Grimsey, Peter D Kirkland, Shaylie Latimore, Stacey E Lynch, Sue Martin, Cornelius Matereke, Peter T Mee, Matthew J Neave, Mark O’Dea, Andrew J Read, Kim O’Riley, Vittoria Stevens, Sivapiragasam Thayaparan, Sara Zufan, Silvia Ban de Gouvea Pedroso, Victoria Grillo, Andrew C Breed, Ian G Barr, Edward C Holmes, Marcel Klaassen, Frank Y K Wong","doi":"10.1093/ve/veae076","DOIUrl":"https://doi.org/10.1093/ve/veae076","url":null,"abstract":"The current panzootic of high pathogenicity avian influenza virus H5N1 demonstrates how viral incursions can have major ramifications for wildlife and domestic animals. Herein, we describe the recent incursion into Australia of two low pathogenicity avian influenza virus subtypes, H4 and H10, that exhibited contrasting evolutionary dynamics. Viruses detected from national surveillance and disease investigations between 2020-2022 revealed 27 genomes, 24 of which have at least one segment more closely related to Eurasian or North American avian influenza lineages than those already circulating in Australia. Phylogenetic analysis revealed that H4 viruses circulating in shorebirds represent a recent incursion from Asia that is distinct from those circulating concurrently in Australian waterfowl. Analysis of the internal segments further demonstrates exclusive, persistent circulation in shorebirds. This contrasts with H10, where a novel lineage has emerged in wild waterfowl, poultry and captive birds across Australia, and has likely replaced previously circulating H10 lineages through competitive exclusion. Elucidating different dynamics for avian influenza incursions supports effective disease risk identification and communication that better informs disease preparedness and response.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"37 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217234","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}
Objectives The classification of the severe fever with thrombocytopenia syndrome virus (SFTSV) lacked consistency due to limited virus sequences used across previous studies, and the origin and transmission dynamics of the SFTSV remains not fully understood. In this study, we analyzed the diversity and phylodynamics of SFTSV using the most comprehensive and largest dataset publicly available for a better understanding of SFTSV classification and transmission. Methods 1,267 L segments, 1,289 M segments, and 1,438 S segments collected from China, South Korea, and Japan were included in this study. Maximum likelihood trees were reconstructed to classify the lineages. Discrete phylogeographic analysis was conducted to infer the phylodynamics of SFTSV. Results We found that the L, M, and S segments were highly conserved, with mean pairwise nucleotide distances of 2.80%, 3.36%, and 3.35% and could be separated into 16, 13, and 15 lineages, respectively. The evolutionary rate for L, M and the S segment was 0.61×10-4 (95% HPD: 0.48–0.73×10-4), 1.31×10-4 (95% HPD: 0.77–1.77×10-4) and 1.27×10-4 (95% HPD: 0.65–1.85×10-4) subs/site/year. The SFTSV most likely originated from South Korea around the year of 1617.6 (95% HPD: 1513.1–1724.3), 1700.4 (95% HPD: 1493.7–1814.0) and 1790.1 (95% HPD: 1605.4–1887.2) for L, M and S segments, respectively. Hubei Province in China played a critical role in the geographical expansion of the SFTSV. The effective population size of SFTSV peaked around 2010 to 2013. We also identified several codons under positive selection in the RdRp, Gn-Gc and NS genes. Conclusions By leveraging the largest dataset of SFTSV, our analysis could provide new insights into the evolution and dispersal of SFTSV, which may be beneficial for the control and prevention of severe fever with thrombocytopenia syndrome.
{"title":"The classification, origin and evolutionary dynamics of severe fever with thrombocytopenia syndrome virus circulating in East Asia","authors":"Shaowei Sang, Peng Chen, Chuanxi Li, Anran Zhang, Yiguan Wang, Qiyong Liu","doi":"10.1093/ve/veae072","DOIUrl":"https://doi.org/10.1093/ve/veae072","url":null,"abstract":"Objectives The classification of the severe fever with thrombocytopenia syndrome virus (SFTSV) lacked consistency due to limited virus sequences used across previous studies, and the origin and transmission dynamics of the SFTSV remains not fully understood. In this study, we analyzed the diversity and phylodynamics of SFTSV using the most comprehensive and largest dataset publicly available for a better understanding of SFTSV classification and transmission. Methods 1,267 L segments, 1,289 M segments, and 1,438 S segments collected from China, South Korea, and Japan were included in this study. Maximum likelihood trees were reconstructed to classify the lineages. Discrete phylogeographic analysis was conducted to infer the phylodynamics of SFTSV. Results We found that the L, M, and S segments were highly conserved, with mean pairwise nucleotide distances of 2.80%, 3.36%, and 3.35% and could be separated into 16, 13, and 15 lineages, respectively. The evolutionary rate for L, M and the S segment was 0.61×10-4 (95% HPD: 0.48–0.73×10-4), 1.31×10-4 (95% HPD: 0.77–1.77×10-4) and 1.27×10-4 (95% HPD: 0.65–1.85×10-4) subs/site/year. The SFTSV most likely originated from South Korea around the year of 1617.6 (95% HPD: 1513.1–1724.3), 1700.4 (95% HPD: 1493.7–1814.0) and 1790.1 (95% HPD: 1605.4–1887.2) for L, M and S segments, respectively. Hubei Province in China played a critical role in the geographical expansion of the SFTSV. The effective population size of SFTSV peaked around 2010 to 2013. We also identified several codons under positive selection in the RdRp, Gn-Gc and NS genes. Conclusions By leveraging the largest dataset of SFTSV, our analysis could provide new insights into the evolution and dispersal of SFTSV, which may be beneficial for the control and prevention of severe fever with thrombocytopenia syndrome.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"16 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217235","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}
Jia-Ying Li, Hao-Yang Wang, Ye-Xiao Cheng, Chengyang Ji, Shenghui Weng, Na Han, Rong Yang, Hang-Yu Zhou, Aiping Wu
The global prevalence of the XBB lineage presents a formidable challenge posed by the recombinant SARS-CoV-2 virus. The understanding of SARS-CoV-2’s recombination preference assumes utmost significance in predicting future recombinant variants and adequately preparing for subsequent pandemics. Thus, an urgent need arises to establish a comprehensive landscape concerning SARS-CoV-2 recombinants worldwide and elucidate their evolutionary mechanisms. However, the initial step, involving the detection of potential recombinants from a vast pool of over ten million sequences, presents a significant obstacle. In this study, we present CovRecomb, a lightweight methodology specifically designed to effectively identify and dissect interlineage SARS-CoV-2 recombinants. Leveraging CovRecomb, we successfully detected 135,567 putative recombinants across the entirety of 14.5 million accessed SARS-CoV-2 genomes. These putative recombinants could be classified into 1,451 distinct recombination events, of which 206 demonstrated transmission spanning multiple countries, continents, or globally. Hotspot regions were identified in six specific areas, with prominence observed in the latter halves of the N-terminal domain and receptor-binding domain within the spike (S) gene. Epidemiological investigations revealed extensive recombination events occurring among different SARS-CoV-2 (sub)lineages, independent of lineage prevalence frequencies.
{"title":"Comprehensive detection and dissection of interlineage recombination events in the SARS-CoV-2 pandemic","authors":"Jia-Ying Li, Hao-Yang Wang, Ye-Xiao Cheng, Chengyang Ji, Shenghui Weng, Na Han, Rong Yang, Hang-Yu Zhou, Aiping Wu","doi":"10.1093/ve/veae074","DOIUrl":"https://doi.org/10.1093/ve/veae074","url":null,"abstract":"The global prevalence of the XBB lineage presents a formidable challenge posed by the recombinant SARS-CoV-2 virus. The understanding of SARS-CoV-2’s recombination preference assumes utmost significance in predicting future recombinant variants and adequately preparing for subsequent pandemics. Thus, an urgent need arises to establish a comprehensive landscape concerning SARS-CoV-2 recombinants worldwide and elucidate their evolutionary mechanisms. However, the initial step, involving the detection of potential recombinants from a vast pool of over ten million sequences, presents a significant obstacle. In this study, we present CovRecomb, a lightweight methodology specifically designed to effectively identify and dissect interlineage SARS-CoV-2 recombinants. Leveraging CovRecomb, we successfully detected 135,567 putative recombinants across the entirety of 14.5 million accessed SARS-CoV-2 genomes. These putative recombinants could be classified into 1,451 distinct recombination events, of which 206 demonstrated transmission spanning multiple countries, continents, or globally. Hotspot regions were identified in six specific areas, with prominence observed in the latter halves of the N-terminal domain and receptor-binding domain within the spike (S) gene. Epidemiological investigations revealed extensive recombination events occurring among different SARS-CoV-2 (sub)lineages, independent of lineage prevalence frequencies.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"25 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217236","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}
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}
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