Virus Evolution最新文献

The hemagglutinin of human influenza virus evolves rapidly to erode neutralizing antibody immunity. Twice per year, new vaccine strains are selected with the goal of providing maximum protection against the viruses that will be circulating when the vaccine is administered ~8-12 months in the future. To help inform this selection, here we quantify how the antibodies in recently collected human sera neutralize viruses with hemagglutinins from contemporary influenza strains. Specifically, we use a high-throughput sequencing-based neutralization assay to measure how 188 human sera collected from Oct 2024 to April 2025 neutralize 140 viruses representative of the H3N2 and H1N1 strains circulating in humans as of the summer of 2025. This data set, which encompasses 26 148 neutralization titre measurements, provides a detailed portrait of the current human neutralizing antibody landscape to influenza A virus. The full data set and accompanying visualizations are available for use in vaccine development and viral forecasting.

The emergence of various SARS-CoV-2 lineages with adaptive mutations is of significant concern worldwide, especially when these mutations enhance the virus's ability to either evade immune responses or transmit more efficiently. Between September and December 2023, a highly diverged BA.2-related lineage, designated BA.2.87.1, was detected through diagnostic testing, syndromic surveillance, and wastewater surveillance in the Limpopo, Mpumalanga, Western Cape, Eastern Cape, and Gauteng provinces of South Africa. This lineage harbours 20 amino acid substitutions in Spike protein relative to baseline BA.2, including at antigenic sites of the receptor-binding domain (including N417T, K444N, V445G, L452M, N460K, K478T, N481K, and R493Q) and, most strikingly, large deletions of the N-terminal domain (NTD) residues 15-26 and 136-146. Such large NTD deletions have never been observed in circulating lineages but do sometimes occur in highly mutated sequences originating in chronic infections. Phylodynamic analysis supports the possibility that the BA.2.87.1 lineage originated in a chronic infection in that the nearest known ancestor of this lineage last circulated at least 18 months prior to its first detection. Although BA.2.87.1 had immune evasion and/or transmission potential, its detection was not associated with a surge of infections and it was displaced by the globally dominant BA.2.86 lineage, JN.1, in the last few weeks of 2023. Our findings further strengthen the case for genomic surveillance through clinical and wastewater surveillance systems. SARS-CoV-2 continues to circulate and evolve within the global population. Multiple divergent Omicron lineages such as BA.1, BA.2, BA.3, BA.4, and BA.5 that have emerged from the southern African region have had a major impact on the epidemiology of the virus worldwide. This is likely driven by the large population of immunocompromised individuals due to the high burden of HIV/AIDS and TB in the region that facilitates long-term chronic infections. This article provides insights into the emergence of the BA.2.87.1 lineage, which briefly circulated in South Africa. The lineage displayed a unique mutational profile, including major substitutions in the receptor-binding domain and N-terminal domain deletions. The study also highlights the critical role of syndromic and wastewater surveillance in monitoring the circulation and evolution of SARS-CoV-2.

Arthropod-borne viruses are a major cause of global viral infections, displaying evolutionary dynamics that differ significantly from vertebrate-specific pathogens. To investigate evolutionary constraints across host environments, we conducted deep mutational scanning (DMS) on the Envelope (E) protein of West Nile virus (WNV), a model arbovirus. Our findings reveal a high degree of constraint in WNV E. While overall tolerance to substitutions is higher in mosquito cells, fitness between mosquito, avian, and human cells is highly correlated. We use our data to explore the extent of antagonistic pleiotropy, or fitness tradeoffs, between the three host environments. We highlight distinct hotspots where tolerance to amino acid substitutions differs, finding that avian cells exhibit particularly distinct mutational tolerance. By examining the distribution of mutational fitness effects of naturally occurring amino acid substitutions, we gain insight into which substitutions can theoretically persist across both mosquito and vertebrate environments. This understanding is crucial for connecting DMS results to the evolutionary potential of arboviruses. Finally, we demonstrate the utility of WNV E DMS in explaining the natural diversity of highly dissimilar flavivirus pathogens. We identify specific sites in each clade of flaviviruses that are not well predicted by our mutational data, due to functional and genetic diversification of E proteins over long-term evolution. This work bridges a key gap in understanding the molecular constraints maintaining infection in distinct host environments. Further, we highlight specific sites in the E protein that require further study to understand the dynamic fitness landscape navigated by the genus Flavivirus.

Lymphocytic choriomeningitis virus (LCMV) is a neglected zoonotic arenavirus primarily transmitted by house mice (Mus musculus). In humans, LCMV infection can cause encephalitis, meningitis, or severe birth defects. In New World (NW) primates, LCMV causes acute and fatal callitrichid hepatitis (CH). We detected a continuous occurrence of LCMV lineages I and II in the house mouse population of a zoo, with the first occurrence of lineage II in 2014 and lineage I in 2021. Although the total LCMV RNA prevalence tended to increase between 2021 and 2023, this was primarily associated with lineage I, while the occurrence of lineage II tended to decrease. Despite both lineages I and II being present in house mice in the same building where NW primates are housed, only lineage II was detected in NW primates with CH, and a wild wood mouse (Apodemus sylvaticus). Genomic assignment detected exclusively M.m. domesticus ancestry in the house mouse population of the zoo, in keeping with a natural origin of house mice from the study region. Therefore, the origin of lineage I is most likely explained by the occurrence of this house mouse subspecies. The origin and incursion mode of lineage II still remain elusive. The detection of three or four LCMV genome segments in several house mice was interpreted as LCMV co-infections, and the emergence of a reassortant virus containing an S-segment of lineage II and an L-segment of lineage I. Full genome sequences showed limited diversity of the 2014 LCMV sequences from NW primates, consistent with a recent introduction of lineage II. LCMV sequences from 2021 to 2023 diverged, not only from those from 2014 but also from each other, which suggests long-term evolution in a large host population and/or potential repeated introductions of LCMV lineage II. In conclusion, the presence of two LCMV lineages within the house mouse population of the zoological garden not only poses a potential health threat for employees and visitors of the zoological garden, and potentially other zoo animals, but also provides a unique opportunity to advance our understanding of arenavirus evolution.

Beneficial mutations drive the within-host adaptation of viral populations and can prolong the duration of host infection. Yet, most mutations are not adaptive and the increase of the mean fitness of viral populations is hampered by deleterious and lethal mutations. Because of this ambivalent role of mutations, it is unclear if a higher mutation rate boosts or slows down viral adaptation. Here, we study the interplay between selection, mutation, genetic drift and within-host dynamics of viral populations. We obtain good approximations for the transient evolutionary epidemiology of viral adaptation under the assumption that the mutation rate is high and the effects of nonlethal mutations remain small. We use measures of fitness effects of mutations for a range of viruses to predict the critical mutation rate required to drive viral extinction. This analysis questions the feasibility of lethal mutagenesis because the fold increase of viral mutation rates induced by available mutagenic drugs is not high enough to reach the critical mutation rate predicted by our model.

The remarkable speed at which viral populations mutate allows them to evolve quickly, so that the viral diversity can change, especially when the virus is transmitted, i.e. its population goes through a bottleneck. Our experiments assessed the diversity of the intra-host populations of a mycovirus Cryphonectria hypovirus 1 (CHV1), a natural biocontrol agent of chestnut blight disease, using PacBio long-read HiFi sequencing. The intra-host viral population diversity before and after either vertical or horizontal transmission was estimated using two metrics-nucleotide (mutational) diversity measured as π, and viral variant diversity measured as Nei's H. A significant bottleneck effect, demonstrated by the decline of the mutational diversity (π), was observed after vertical transmission of prototypical viral populations into conidia, in both investigated viral subtypes, French 1 (F1) and Italian (I). In contrast, the number of viral variants was significantly reduced after the vertical transmission of subtype I but increased for the subtype F1. In newly isolated fungal strains infected with CHV1 subtype I, fewer viral variants were vertically transferred into conidia, relative to the prototypical laboratory isolates, i.e. the average number of transmitted viral variants was smaller. In the horizontal viral transmission assays, the number of transmitted viral variants was closely linked to the genotype of the fungal host at the vegetative compatibility loci. Specifically, recipient viral populations' diversity was greater when the alleles at loci vic2 and vic3 were the same in the donor and recipient fungal isolate, relative to when they were different. Heteroallelism at the vic4 locus had no impact on viral populations' diversity. Despite the strong bottlenecks, purifying selection shaped the diversity of intra-host CHV1 populations. In both transmission experiments on average, synonymous mutational diversity was higher than non-synonymous, across all replicates. Signs of positive selection or mutation accumulations, inferred by a surplus of nonsynonymous mutations, were less common and mostly observed during vertical transmission experiments, i.e. in new viral populations arising from conidia.

Evaluating travel restriction effectiveness in mitigating infectious disease burden, exemplified by COVID-19, is critical for informing pandemic response policy, yet methodologies and results evaluating their effectiveness vary considerably. We hypothesized Canadian COVID-19 travel restrictions, including flight bans and enhanced screening, targeting focal source countries where SARS-CoV-2 variants of concern (VOCs) Alpha, Beta, Gamma, Delta, and Omicron were first identified, were variably effective towards averting introductions and case burden. We conducted a retrospective observational study using all the publicly available SARS-CoV-2 sequences and COVID-19 diagnoses up to March 2022, after which polymerase chain reaction (PCR) testing and surveillance sequencing decreased. Average daily variant cases were estimated across global regions and Canadian provinces, which informed subsampling probabilities for sequences for up to 50 000 sequences for VOCs and variants of interest from late 2020 to early 2022. Maximum likelihood phylogeographic methods were used to infer Canadian SARS-CoV-2 sublineages and singletons, representing international viral introductions with and without domestically sampled descendants. Reduction of sublineage and singleton introduction rates and proportional contributions from focal sources were quantified following interventions' introductions. Sublineages and cases averted via VOC travel restrictions were estimated based on sublineages' introduction rates and growth characteristics prior to restrictions. Our results suggest that across VOCs subject to targeted travel restrictions, approximately 995 (841-1151) introductions may have been prevented, accounting for an averted burden of 971 371 (321 204-1 004 575) cases, 10 685 (3533-11 050) hospitalizations, and 561 (185-580) deaths, largely accounted for by the Delta-related India flight ban. However, these estimates represent an upper bound of effectiveness if any assumptions were violated, including that introductions can be treated as independent when susceptibility is high, averted introductions mirror characteristics of observed introductions, and that travel restrictions caused sustained changes in travel behaviour. Travel restrictions were most effective when implemented rapidly following variant emergence, during exponential case growth in the focal source country, and concurrent with limited domestic and global circulation. Our analyses suggest that COVID-19 travel restrictions, particularly flight suspensions, mitigated variant case burden when global circulation was limited and case burden was high in the focal source, and highlight their value in future pandemic response, although public health benefits must be weighed against socioeconomic costs.

[This corrects the article DOI: 10.1093/ve/veac022.].

While intra-host evolution of arboviruses in mosquitoes has been documented, studies of insect-specific viruses (ISVs) remain limited. This study examines evolutionary patterns [i.e. evolutionary process, mutational types (synonymous/nonsynonymous)] of the cell-fusing agent virus (CFAV), an ISV that infects adult Aedes aegypti, over a period of 21 days post-infection (dpi), with a focus on the relationship between viral population dynamics and genetic diversity. High-throughput sequencing of amplification products covering the entire viral genome revealed a significant positive correlation of CFAV genetic diversity with viral population size and natural selection ([Formula: see text]/[Formula: see text]). Notably, diversity for both synonymous and nonsynonymous single nucleotide variant (SNV) sites displayed a positive correlation with population size and natural selection suggesting that genetic drift and purifying selection contribute to the overall outcome of genetic diversity. Additionally, we confirmed that smaller viral population sizes lead to greater temporal changes in genetic structure, particularly evident between Day 1 dpi and Day 3 dpi when genetic drift was most pronounced. We found that non-structural (NS) genes accumulated a higher frequency of synonymous SNV sites than structural genes, likely due to reduced selection pressure acting on NS genes. In contrast, structural genes, particularly the E gene, are likely to exhibit strong selective pressure, as indicated by a significant frequency of nonsynonymous SNV sites. Overall, this study elucidated the evolutionary patterns of CFAV, highlighting the roles of reduced genetic drift as influenced by population size and purifying selection in shaping the overall genetic diversity-and possibly adaptive evolution within structural genes, such as the E gene.