Virus EvolutionPub Date : 2025-08-30eCollection Date: 2025-01-01DOI: 10.1093/ve/veaf065
Sanni Översti, Emily Gaul, Björn-Erik Ole Jensen, Denise Kühnert
{"title":"Phylogenetic meta-analysis of persistent SARS-CoV-2 infections in immunocompromised individuals highlights the challenges of robust evolutionary rate estimation caused by low genetic diversity.","authors":"Sanni Översti, Emily Gaul, Björn-Erik Ole Jensen, Denise Kühnert","doi":"10.1093/ve/veaf065","DOIUrl":"10.1093/ve/veaf065","url":null,"abstract":"<p><p>Time-stamped genomic sequences from rapidly evolving pathogens can be used to estimate the rates of evolution through molecular tip-dating. The validity of this approach, however, depends on whether detectable levels of genetic variation have accumulated over the given sampling interval, generating a temporal signal. Moreover, molecular dating methods have demonstrated varying degrees of systematic biases under different biologically realistic scenarios, such as the presence of phylo-temporal clustering. Persistent SARS-CoV-2 infections in immunocompromised individuals have been linked to accelerated intrahost molecular rates compared to those of global lineages, facilitating the emergence of novel viral lineages. Yet, studies reporting elevated rates lack assessment of data properties, such as evaluation of temporal signal and comparison of multiple methods of inference, both crucial for robust rate estimation. In this study, we applied a range of molecular dating approaches to reassess the rate of SARS-CoV-2 intrahost evolution in immunocompromised individuals using publicly available datasets. Our findings suggest that even during long-term infections, the limited number of genetic changes accumulating may pose a challenge for robust inference of within-host evolutionary rates, particularly when relying on consensus sequences and when datasets are small or unevenly sampled. Moreover, our results highlight that when certain methodological limitations are overlooked, evolutionary rates can be significantly overestimated. In general, our findings demonstrate that estimating within-host evolutionary rates is a challenging question necessitating thorough assessment of data quality, careful selection of appropriate methods, and cautious interpretation of the resulting estimates. Whereas our phylogenetic analyses of viral consensus sequences provide no evidence of elevated evolutionary rates across the complete genome during chronic SARS-CoV-2 infection, prolonged viral shedding may nevertheless promote the emergence of new viral variants in immunocompromised individuals.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veaf065"},"PeriodicalIF":4.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202226","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}
Virus EvolutionPub Date : 2025-08-23eCollection Date: 2025-01-01DOI: 10.1093/ve/veaf064
Stephanie Bellman, Nima Shariatzadeh, Tyshawn Ferrell, Audrey Long, Leah Aeschleman, Ellie Fausett, Tim Walsh, Seana Cleary, Isabella Roeske, Erick Ojeda, Madison Schwab, Hannah Dakanay, Sam R Telford Iii, Heidi K Goethert, Gonzalo Vazquez-Prokopec, Anne Piantadosi
{"title":"Focal persistence and phylodynamics of Heartland virus in Georgia.","authors":"Stephanie Bellman, Nima Shariatzadeh, Tyshawn Ferrell, Audrey Long, Leah Aeschleman, Ellie Fausett, Tim Walsh, Seana Cleary, Isabella Roeske, Erick Ojeda, Madison Schwab, Hannah Dakanay, Sam R Telford Iii, Heidi K Goethert, Gonzalo Vazquez-Prokopec, Anne Piantadosi","doi":"10.1093/ve/veaf064","DOIUrl":"10.1093/ve/veaf064","url":null,"abstract":"<p><p>Heartland virus (HRTV) is an emerging tick-borne virus associated with severe illness in the USA. There are large gaps in knowledge of HRTV diversity, evolution, and transmission due to a paucity of HRTV-positive samples and genome sequences. We identified a focal site of HRTV-positive <i>Amblyomma americanum</i> ticks in central Georgia and developed a novel multiplex-amplicon sequencing assay to generate full HRTV genome sequences. By screening over 21 000 field-collected ticks from 2021 to 2023, we identified six positive pools. Five were collected from the site in central Georgia where our group first detected HRTV-positive ticks in 2019 and one from a site in western Georgia ~175 km away. The HRTV genome sequences from Georgia were highly related, even across this distance and over five years. Reference HRTV genome sequences from across the USA were also geographically clustered. Time-scaled phylogenetic analysis suggested a recent spread of HRTV in the USA, with all available sequences sharing a common ancestor within the last 75 years, since the mid-1900s, and sequences from Georgia sharing a common ancestor within the last 15 years, since 2010. Our observed spatial clustering of HRTV and the high degree of genetic conservation in our persistent focus suggest the importance of small spatial dynamics in HRTV transmission ecology.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veaf064"},"PeriodicalIF":4.0,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139503","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}
Virus EvolutionPub Date : 2025-08-22eCollection Date: 2025-01-01DOI: 10.1093/ve/veaf063
Cinzia Borgogna, Ilaria Cislaghi, Sarah Turati, Alessandra Mozzi, Diego Forni, Rachele Cagliani, Manuela Sironi, Marisa Gariglio
{"title":"Convergent evolution of the G3BP1-binding motif in betacoronavirus nucleocapsid proteins.","authors":"Cinzia Borgogna, Ilaria Cislaghi, Sarah Turati, Alessandra Mozzi, Diego Forni, Rachele Cagliani, Manuela Sironi, Marisa Gariglio","doi":"10.1093/ve/veaf063","DOIUrl":"10.1093/ve/veaf063","url":null,"abstract":"<p><p>Betacoronaviruses (β-CoVs) display divergent mechanisms to evade host antiviral responses, yet the evolutionary origin and functional relevance of their strategies remain unclear. Stress granules (SGs), central to host defenses, are disrupted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein <i>via</i> its interaction with G3BP1 mediated by an <sup>15</sup>ITFG<sup>18</sup> motif. This interaction inhibits SG assembly, enhancing viral replication and immune evasion. Here, we analyzed 179 N protein sequences across β-CoVs subgenera and identified the ITFG motif in sarbecoviruses but not in MERS-CoV or embecoviruses. Among tested CoVs, only SARS-CoV-2 N showed robust G3BP1 binding <i>in vitro</i> and in infected cells. Phylogenetic analyses revealed that the ΦxFG motif emerged independently in sarbecoviruses and a bat-infecting merbecovirus clade. The VGTF motif in these merbecoviruses also binds to G3BP1, suggesting convergent evolution in viral evasion strategies. The emergence of this motif was unrelated to 4a protein inactivation, another viral protein that inhibits SG formation.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veaf063"},"PeriodicalIF":4.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042373","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}
Virus EvolutionPub Date : 2025-08-05eCollection Date: 2025-01-01DOI: 10.1093/ve/veaf059
Chelsea Cereghino, Kateland Tiller, Lin Kang, Pawel Michalak, James Weger-Lucarelli
{"title":"The recurrent Spike A222V mutation in SARS-CoV-2 enhances replication in primary deer lung cells.","authors":"Chelsea Cereghino, Kateland Tiller, Lin Kang, Pawel Michalak, James Weger-Lucarelli","doi":"10.1093/ve/veaf059","DOIUrl":"10.1093/ve/veaf059","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects humans and animals and is therefore a pathogen of grave concern within a One Health framework. Identifying animal-adaptive mutations is critical to preserving One Health, as these mutations could also lead to the persistence of SARS-CoV-2 in animal reservoirs with continual spillover to humans. Therefore, we sought to pair experimental evolution and epidemiological data to identify putative human- and animal-adaptive viral residues and determine their impact on replication-competent SARS-CoV-2 in both human and animal cells. We passaged SARS-CoV-2 in cells expressing human, dog, cat, mink, and white-tailed deer ACE2 and sequenced the passaged populations. In addition, we searched SARS-CoV-2 sequences for mutations following patterns of convergent evolution that were common to both human- and animal-derived SARS-CoV-2 sequences. We identified the epidemiologically relevant Spike A222V mutation from our passaging experiment in cells expressing cat ACE2, a mutation that has also arisen independently across eight lineages of SARS-CoV-2 from human- and animal-derived sequences. To assess its impact on replication in human and animal cells, we constructed SARS-CoV-2 Spike A222V in the Wuhan-Hu-1 backbone with Spike D614G; this virus replicated similarly to the WT SARS-CoV-2 in human lung epithelial cells. In contrast, SARS-CoV-2 Spike A222V demonstrated an advantage in replication in primary deer lung cells, which was not mediated by the deer ACE2 receptor. Infection <i>via</i> the human, dog, cat, and mink ACE2 receptor resulted in reduced replication of SARS-CoV-2 Spike A222V. Our experiments identified Spike A222V as a putatively deer-adaptive mutation. Future studies should assess Spike A222V's relevance to transmission within deer and to other animal species in contact with deer.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veaf059"},"PeriodicalIF":4.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979938","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}
Virus EvolutionPub Date : 2025-08-04eCollection Date: 2025-01-01DOI: 10.1093/ve/veaf058
Jordan T Ort, Samuel S Shepard, Sonja A Zolnoski, Tommy T-Y Lam, C Todd Davis, Richard A Neher, Louise H Moncla
{"title":"Development of avian influenza A(H5) virus datasets for Nextclade enables rapid and accurate clade assignment.","authors":"Jordan T Ort, Samuel S Shepard, Sonja A Zolnoski, Tommy T-Y Lam, C Todd Davis, Richard A Neher, Louise H Moncla","doi":"10.1093/ve/veaf058","DOIUrl":"10.1093/ve/veaf058","url":null,"abstract":"<p><p>The 2022 panzootic of highly pathogenic avian influenza (HPAI) A(H5) viruses has led to unprecedented transmission to multiple mammalian species. Avian influenza A viruses of the H5 subtype circulate globally among birds and are classified into distinct clades based on their haemagglutinin (HA) genetic sequences. Thus, the ability to accurately and rapidly assign clades to newly sequenced isolates is key to surveillance and outbreak response. Cocirculation of endemic, low-pathogenicity avian influenza (LPAI) A(H5) lineages in North American and European wild birds necessitates the ability to rapidly and accurately distinguish between infections arising from these lineages and epizootic HPAI A(H5) viruses. However, currently available clade assignment tools are limited and often require command-line expertise, hindering their utility for public health surveillance labs. To address this gap, we have developed datasets to enable A(H5) clade assignments with Nextclade, a drag-and-drop tool originally developed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic clade classification. Using annotated reference datasets for all historical A(H5) clades, clade 2.3.2.1 descendants, and clade 2.3.4.4 descendants provided by the Food and Agriculture Organization/World Health Organization/World Organisation for Animal Health H5 Working Group, we identified clade-defining mutations for every established clade to enable tree-based clade assignment. We then created three Nextclade datasets which can be used to assign clades to A(H5) HA sequences and call mutations relative to reference strains through a drag-and-drop interface. Nextclade assignments were benchmarked with 19 834 unique sequences not in the reference set using a prereleased version of LABEL, a well-validated and widely used command-line software. Prospective assignment of new sequences with Nextclade and LABEL produced very well-matched assignments (match rates of 97.8% and 99.1% for the 2.3.2.1 and 2.3.4.4 datasets, respectively). The all-clades dataset also performed well (94.8% match rate) and correctly distinguished between all HPAI and LPAI strains. This tool additionally allows for the identification of polybasic cleavage site sequences and potential N-linked glycosylation sites. These datasets therefore provide an alternative, rapid method to accurately assign clades to new A(H5) HA sequences, with the benefit of an easy-to-use browser interface.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veaf058"},"PeriodicalIF":4.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979934","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}
Virus EvolutionPub Date : 2025-08-04eCollection Date: 2025-01-01DOI: 10.1093/ve/veaf060
Dan-Shu Wang, Ying-Ying Zou, Qian Liu, Hao Huang, Pei-Yu Han, Jun-Ying Zhao, Li-Dong Zong, Ye Qiu, Yun-Zhi Zhang, Xing-Yi Ge
{"title":"Sustained cross-species transmission of gammacoronavirus in wild birds revealed by viral characterization in China.","authors":"Dan-Shu Wang, Ying-Ying Zou, Qian Liu, Hao Huang, Pei-Yu Han, Jun-Ying Zhao, Li-Dong Zong, Ye Qiu, Yun-Zhi Zhang, Xing-Yi Ge","doi":"10.1093/ve/veaf060","DOIUrl":"10.1093/ve/veaf060","url":null,"abstract":"<p><p><i>Gammacoronavirus</i> (γ-CoV) primarily infects poultry, wild birds, and marine mammals. The widespread distribution and circulation of γ-CoV in the ecological environment may lead to sustained transmission and economic loss. To better understand the diversity of γ-CoV in wild birds, we collected 482 wild-bird faecal samples from Yunnan, encompassing 14 bird species. We detected 12 γ-CoV-positive samples in five bird species, characterized five complete genomes-HNU5-1, HNU5-2, HNU5-3, HNU6-1, and HNU6-2-and proposed that these genomes represent two viral species. The HNU5 strains were derived from black-headed gull (<i>Chroicocephalus ridibundus</i>), while the HNU6 strains came from mallard (<i>Anas platyrhynchos</i>), and both of those were recombinant. The HNU5 strain exhibited the highest sequence identity (~95%) with a γ-CoV strain isolated from <i>Numenius phaeopus</i> (GenBank accession: PP845452). Similarly, the HNU6 strain showed 95% nucleotide identity with a γ-CoV strain (GenBank accession: PP845437) derived from <i>A. platyrhynchos</i>. Taxonomic analysis confirmed that HNU6s belong to the <i>Gammacoronavirus anatis</i> species, while HNU5s are attributed to a new species. Cross-species analysis revealed active host-switching events among γ-CoVs, indicating potential transmission of γ-CoVs from marine mammals to wild bird and from wild bird to poultry, and inter-wild bird and interpoultry transmission. In summary, we report five new γ-CoV strains in wild birds and outline the cross-species transmission of γ-CoVs. Our findings link γ-CoV hosts across different natural environments and provide new insights for exploring γ-CoVs.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veaf060"},"PeriodicalIF":4.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014509","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}
Virus EvolutionPub Date : 2025-07-25eCollection Date: 2025-01-01DOI: 10.1093/ve/veaf055
Baoding Chen, Yachao Zuo, Yanrong Lv, Hao Zhang, Jiawen Yang, Yun Gu, Junxiong Yang, Meijin Yuan, Kai Yang
{"title":"Revealing the potential transmission route of Cnaphalocrocis medinalis granulovirus capable of persistently causing granulosis epidemics.","authors":"Baoding Chen, Yachao Zuo, Yanrong Lv, Hao Zhang, Jiawen Yang, Yun Gu, Junxiong Yang, Meijin Yuan, Kai Yang","doi":"10.1093/ve/veaf055","DOIUrl":"10.1093/ve/veaf055","url":null,"abstract":"<p><p>As crucial regulators of insect populations in nature, baculoviruses are promising biopesticides. However, due to the scarcity of individuals with overt disease and the sporadic nature of the epidemic, our knowledge of baculovirus ecology is very limited, which impacts the effective utilization of these viruses in biocontrol. Cnaphalocrocis medinalis granulovirus (CnmeGV) specifically infects the rice leaffolder, which is the main pest of rice. In this study, we identified a population of CnmeGV that can cause a persistent epizootic in Dahuai town, Enping County, Guangdong Province, China. We sequenced the whole genomes of 138 CnmeGV isolates collected from Dahuai town for four years, reporting for the first time the genetic structure of a natural population of baculovirus. The results indicated that a long-term endemic population of CnmeGV displayed substantial genetic variation. The discriminant analysis of principal components revealed that the genetic structure of CnmeGV is clearly differentiated annually and seasonally (by the rice-growing season). CnmeGV epidemics typically occur in three waves (W1, W2, and W3) during each rice-growing season. Although the genetic structures of the CnmeGV isolates within the same rice-growing season were closely related, nucleotide diversity analysis revealed that the CnmeGV genomes exhibit higher heterozygosity levels in the initial epidemic wave compared to subsequent waves. We also found that host behaviour, virus distribution, plant structure, and weather are important factors in the recurrence of CnmeGV epizootics. Leveraging these ecological insights, we revealed the potential transmission route of CnmeGV, named 'From W1 in sheath to W2+ in fold', during continuous epidemics in natural environments. This study provides important insights into the ecology and evolution of host-pathogen interactions and the route helps develop more effective biocontrol strategies.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veaf055"},"PeriodicalIF":4.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979913","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}
Virus EvolutionPub Date : 2025-07-25eCollection Date: 2025-01-01DOI: 10.1093/ve/veaf052
Harriet Longley, David Bonsall, Joshua Herbeck, George MacIntyre-Cockett, Sandra E Chaudron, Laura Thomson, Nicholas Grayson, Andrew Mujugira, Christophe Fraser, Jairam Lingappa, Katrina Lythgoe
{"title":"Estimates of HIV-1 within-host recombination rates across the whole genome.","authors":"Harriet Longley, David Bonsall, Joshua Herbeck, George MacIntyre-Cockett, Sandra E Chaudron, Laura Thomson, Nicholas Grayson, Andrew Mujugira, Christophe Fraser, Jairam Lingappa, Katrina Lythgoe","doi":"10.1093/ve/veaf052","DOIUrl":"10.1093/ve/veaf052","url":null,"abstract":"<p><p>Recombination plays a pivotal role in generating within-host diversity and enabling HIV's evolutionary success, particularly in evading the host immune response. Despite this, the variability in recombination rates across different settings and the underlying factors that drive these differences remain poorly understood. In this study, we analysed a large dataset encompassing hundreds of untreated, longitudinally sampled infections using both whole-genome long-read and short-read sequencing datasets. By quantifying recombination rates, we uncover substantial variation across subtypes, viral loads, and stages of infection. We also map recombination hot and cold spots across the genome using a sliding window approach, finding that previously reported inter-subtype regions of high or low recombination are replicated at the within-host level. Importantly, our findings reveal the significant influence of selection on recombination, showing that the presence and success of recombinant genomes is strongly interconnected with the fitness landscape. These results offer valuable insights into the contribution of recombination to evolutionary dynamics and demonstrate the enhanced resolution that long-read sequencing offers for studying viral evolution.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veaf052"},"PeriodicalIF":4.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755212","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}
Virus EvolutionPub Date : 2025-07-22eCollection Date: 2025-01-01DOI: 10.1093/ve/veaf056
Nakarin Pamornchainavakul, Igor A D Paploski, Dennis N Makau, Julia P Baker, Jing Huang, Clarissa P Ferreira, Cesar A Corzo, Albert Rovira, Maxim C-J Cheeran, Samantha Lycett, Andrea Doeschl-Wilson, Declan C Schroeder, Kimberly VanderWaal
{"title":"Experimental evidence of vaccine-driven evolution of respiratory syndrome virus type 2.","authors":"Nakarin Pamornchainavakul, Igor A D Paploski, Dennis N Makau, Julia P Baker, Jing Huang, Clarissa P Ferreira, Cesar A Corzo, Albert Rovira, Maxim C-J Cheeran, Samantha Lycett, Andrea Doeschl-Wilson, Declan C Schroeder, Kimberly VanderWaal","doi":"10.1093/ve/veaf056","DOIUrl":"10.1093/ve/veaf056","url":null,"abstract":"<p><p>Despite extensive use of vaccination, porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2) continues to evolve, likely driven by escape from natural or vaccine-derived immunity. However, direct evidence of vaccine-induced evolutionary pressure remains limited. Here, we tracked the evolution of PRRSV-2 sublineage 1A strain IA/2014 (variant 1A-unclassified) genome from infection chains of sequentially infected pigs under different immune conditions. Weaned pigs were divided into three groups: a non-immunized control group and two groups vaccinated with different modified live virus (MLV) vaccines, namely Prevacent® PRRS MLV (variant 1D.2) and Ingelvac PRRS® MLV (variant 5A.1). Sixty-four days post-vaccination, the pigs were challenged with IA/2014 PRRSV-2. Virus infection chains (which used serum from pigs in batch <i>n</i> to infect batch <i>n</i> + 1) were maintained across six sequential batches of roughly seven pigs each, allowing for virus evolution to occur across the ~ 84 days of the infection chain. A total of 110 serum samples were successfully sequenced. Vaccinated groups exhibited over twice the genetic divergence from the original challenge virus (0.3%-0.4% mean nucleotide distance) compared to non-immunized group (0.15%). Variability was concentrated in ORF1a and ORF1b. Deep sequencing revealed more rapid shifts of viral quasispecies composition in vaccinated pigs, and more homogeneous viral populations over batches compared to non-immunized pigs. Selection pressure analyses indicated strong purifying selection in one vaccinated group, though without clear signals at known antigenic sites in all treatment groups. However, vaccinated pigs had significantly higher cycle threshold values (<i>P</i><.001), indicating lower viral loads and suggesting potential fitness limitations for highly diverged viruses in immunized pigs. These findings demonstrate that MLV vaccination can exert substantial evolutionary pressure on PRRSV-2, driving genetic diversification and highlighting the need for continuous PRRS monitoring and adaptive control strategies.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veaf056"},"PeriodicalIF":4.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884346","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}
Virus EvolutionPub Date : 2025-07-21eCollection Date: 2025-01-01DOI: 10.1093/ve/veaf054
Amber Coats, Yintong R Wang, Katia Koelle
{"title":"Immune pressure is key to understanding observed patterns of respiratory virus evolution in prolonged infections.","authors":"Amber Coats, Yintong R Wang, Katia Koelle","doi":"10.1093/ve/veaf054","DOIUrl":"10.1093/ve/veaf054","url":null,"abstract":"<p><p>Analyses of viral samples from prolonged SARS-CoV-2 infections as well as from prolonged infections with other respiratory viruses have indicated that there are several consistent patterns of evolution observed across these infections. These patterns include accelerated rates of nonsynonymous substitution, viral genetic diversification into distinct lineages, parallel substitutions across infected individuals, and heterogeneity in rates of antigenic evolution. Here, we use within-host model simulations to explore the drivers of these intrahost evolutionary patterns. Our simulations build on a tunably rugged fitness landscape model to first assess the role that mutations that impact only viral replicative fitness have in driving these patterns. We then further incorporate pleiotropic sites that jointly impact replicative fitness and antigenicity to assess the role that immune pressure has on these patterns. Through simulation, we find that the empirically observed patterns of viral evolution in prolonged infections cannot be robustly explained by viral populations evolving on replicative fitness landscapes alone. Instead, we find that immune pressure is needed to consistently reproduce the observed patterns. Moreover, our simulations show that the amount of antigenic change that occurs is higher when immune pressure is stronger and at intermediate immune breadth. While our simulation models were designed to shed light on drivers of viral evolution in prolonged infections with respiratory viruses that generally cause acute infection, their structure can be used to better understand viral evolution in other acutely infecting viruses such as noroviruses that can cause prolonged infection as well as viruses such as HIV that are known to chronically infect.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"11 1","pages":"veaf054"},"PeriodicalIF":4.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884358","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}