Virus Evolution最新文献

In 2023, the US Food and Drug Administration approved the use of nirsevimab for the prevention of respiratory syncytial virus (RSV) infections in healthy infants. This marks an important milestone for using passive immunotherapy for the prevention of viral infections. Previous studies that examined RSV-A sequences from breakthrough infection of nirsevimab-treated infants indicated that the nirsevimab binding site in the RSV-A F protein remained intact. To explore possible nirsevimab-resistant mutations that occur outside the antibody binding site, we have dissected the RSV-A mutations landscape at a single-genome resolution following exposure to nirsevimab. We identified a single amino acid substitution (S190R) at the antigenic site V of the RSV-A F protein that emerged in the vast majority of the isolated viruses. We further demonstrated that the S190R mutation reduces the binding and neutralization capacity of nirsevimab by altering antibody accessibility to site Ø epitopes. Additionally, by analysing the replication of S190R RSV-A in cell lines and in primary human organoids, we illustrated that the S190R mutation impairs the viral fitness of RSV-A. Thus, our study provides insight into possible viral mechanisms that can contribute to RSV-A escape from nirsevimab-based immunization.

African Swine Fever virus has become a primary concern for veterinarian health agencies and pig producers worldwide. The current panzootic of the virus genotype II is having a devastating impact on pig production in Africa, Europe, Asia, Oceania, and Hispaniola (Caribbean). Due to its high persistence and mortality rate, disease control policies require enhanced passive surveillance, wild boar depopulation, containment, and other costly interventions, as a safe and effective vaccine is not currently available. Since 2007, several disease clusters have emerged far from both its original range (South-Eastern Africa) and from other affected suid populations. These transmissions were likely caused by anthropogenic movement, facilitated by the virus persistence in the environment and on contaminated material. The objective of this research was to understand the spatio-temporal dynamics of the African Swine Fever virus panzootic, with a specific focus on clusters from mainland Italy. We mapped and analysed the virus spread using 228 whole-genome sequences available from online repositories and from the Italian cases/outbreaks, combined with their metadata. We inferred pathogen phylogenies using a Bayesian phylodynamic model, with which we obtained a time-scaled and spatially explicit maximum clade credibility tree. Our results indicate that the Eurasian genotype II panzootic originated in Africa around 20 years ago (September 2003-May 2007) and showed long-distance transmissions across regions or continents within a short time frame, including from Europe to East Asia and from South-Eastern to Western Africa. Dense local dynamics, particularly in areas where the disease affected a naïve population, were also observed. The distribution of spatial distances inferred along the trees' branches further highlighted these trends and revealed how previously observed survival times in pork products could allow the virus to traverse distances up to 900 km (in 137 days). Finally, from the available data, we identified at least seven separate introductions in Europe, of which at least three caused new clusters on mainland Italy. This study provides important insights on the African Swine Fever virus introduction into many affected areas worldwide and highlights the crucial role of genomic surveillance in correctly tracking the pathogen spread and monitoring the virus potential evolution.

RNA viruses exhibit a high mutation rate, contributing to their genetic diversity mainly because their RNA polymerase lacks proofreading ability. Arboviruses, which alternate between vertebrate and invertebrate hosts, are subjected to host-specific selective pressures and population bottlenecks, mainly within mosquito vectors. Although experimental studies have brought insights into their evolutionary dynamics, data from naturally infected vectors remain limited. Here, we investigated the intrahost genetic diversity of chikungunya virus (CHIKV-ECSA lineage) through whole-genome sequencing of 19 human- and 19 mosquito-derived genomes from the 2024 outbreak in São José do Rio Preto, Brazil. Our principal component analysis revealed a greater mutation number in mosquito-derived genomes, predominantly driven by low-frequency and unique variants. Overall, intrahost genetic diversity was significantly higher in mosquito-derived than in human-derived CHIKV genomes, and protein-coding regions showed host-specific patterns. We identified 303 mutations across all CHIKV genomes. Interestingly, shared mutations were predominantly classified as synonymous, whereas unique mutations were mainly nonsynonymous. Gene-wide selection analyses indicated that purifying selection predominates across CHIKV genomes from both humans and mosquitoes, suggesting that most mutations, particularly nonsynonymous ones, are deleterious and subject to purifying selection. However, in mosquito-derived CHIKV genomes, evidence of relaxed purifying selection and neutral evolution, in specific proteins, such as E3 and NSP3, respectively, was observed, in contrast to the stronger purifying selection observed in human-derived CHIKV sequences. Site-specific selection analyses corroborated these results, detecting negatively selected sites in human-derived genomes but not in mosquito-derived genomes for these specific proteins. Together, our results show that these host-specific differences enable mosquitoes to act as reservoirs of genetic diversity by maintaining nonsynonymous variants, likely driven by genetic drift. At the same time, human hosts may impose stronger selective pressures, contributing to preserving the genome stability. This dynamic balance between diversification in vector populations and selective constraints in vertebrate hosts likely drives CHIKV evolution and adaptation.

Cotesia chilonis, a key parasitoid wasp of the important rice pest Chilo suppressalis, plays a critical role in the biological control of its host larvae. While previous studies have predominantly focused on polydnaviruses, associated with this species, the RNA virome of C. chilonis remains largely uncharacterized. To address this gap, we conducted a comprehensive viromic analysis across 17 geographically distinct populations of C. chilonis, identifying nine novel RNA viruses phylogenetically affiliated with eight families: Xinmoviridae, Artoviridae, Rhabdoviridae, Qinviridae, Orthomyxoviridae, Phenuiviridae, Narnaviridae, and Virgaviridae. These viruses include seven negative-sense single-stranded RNA (-ssRNA) viruses and two positive-sense single-stranded RNA (+ssRNA) viruses. Analysis of their geographic distribution revealed significant distribution patterns, with two -ssRNA viruses (C. chilonis Xinmo-like virus, CcXLV, and C. chilonis Arto-like virus, CcALV) demonstrating broad prevalence and stable spatiotemporal persistence. This study not only expands the diversity of RNA viruses in parasitoid wasps but also provides foundational insights into potential virus-host interactions, offering potential avenues for optimizing parasitoid-based pest management strategies.

The pathogens of hand, foot, and mouth disease (HFMD) are changing, with CV-A6 becoming the predominant one and evolving rapidly. We collected data on monthly HFMD infections per county and related demographic variables in Shandong Province, China, during 2023. Viruses were isolated and sequenced for further bioinformatics analysis. An epidemiological follow-up study in Jinan city was conducted to explore the relationship between onychomadesis and CV-A6. The risk factors of atypical skin lesions were analysed using binary logistic regression models. Totally, 47 396 cases were clinically diagnosed as HFMD, among which 9543 samples were collected and 7133 (74.75%) were laboratory-confirmed Enterovirus (EV)-positive cases. CV-A6 became the predominant pathogen (5993, 84.02%). Forty-six representative CV-A6 strains were successfully isolated; by successfully constructing a novel amplicon-based next-generation sequencing method, the full genomes of the 46 strains were sequenced. All strains belonged to the D3c subgenotype. A new recombination lineage emerged with three specific amino acid mutations in the P3 region. Fourteen amino acid sites in the P3 coding region and three in the VP1 coding region were identified as highly variable amino acid sites. On the whole, viral evolution was predominantly driven by negative selection. Three amino acid sites in the VP1 coding region and one in the P3 coding region were under positive selection, among which P3-551 was both a highly variable amino acid site and underwent positive selection pressure. CV-A6 strains in Shandong, 2023, may have originated from Southwest China lineages, which emerged from Vietnam. CV-A6 was the primary pathogen of onychomadesis and atypical skin lesions. The increase in age, male individuals, living in suburban areas, with fever and respiratory symptoms were significant risk factors for atypical skin lesions. In 2023, CV-A6 was the predominant pathogen of HFMD in Shandong and underwent rapid evolution with frequent recombination and mutations. Therefore, surveillance for disease prevention and control should be strengthened.

Phage lifestyles impose distinct selective pressures on genome architecture and codon usage. This study compares gene length and codon usage patterns in Listeria monocytogenes phages, analysing 686 temperate and 1516 virulent phages coding sequences. Most temperate phages had significantly smaller genomes (41 022.5 ± 3225.2 kb) and shorter genes (555 ± 647.1 nt) than virulent phages (101 089.3 ± 44 030.4 kb; 629 ± 583.5 nt). Codon adaptation was higher in the temperate phages [codon adaptation index (CAI) = 0.711 ± 0.045 vs. 0.679 ± 0.047; P < 1.4 × 10^-51], while codon usage bias was stronger in the virulent phages (effective number of codons = 44.80 ± 5.863 vs. 46.00 ± 6.647; P < 1.0 × 10^-7), which also had higher guanine and cytosine (GC) content (35.84 ± 2.985% vs. 35.21 ± 3.791%). CAI and %GC3 correlated strongly (r = -0.77 to -0.97) genome-wide. These results demonstrate that L. monocytogenes phage lifestyle shapes codon usage through distinct strategies of host adaptation and translational optimization. Also importantly, these findings can advance the development of biotechnological and synthetic biology tools for improving rapid determination of lifestyle of phages and their use in therapeutic and biocontrol applications.

Background: Human enteric species F adenoviruses are a leading cause of diarrhoea-associated paediatric morbidity and mortality worldwide. The cellular immune response (antigen-specific cytotoxic T cells and secreted cytokines) to human adenovirus (HAdV) infection is known to ameliorate symptoms and is critical for viral clearance. We hypothesized that the capsid proteins (hexon and penton) of HAdV-F40 and 41 (F40, F41) are evolving to escape cellular immune responses. Major histocompatibility complex (MHC) binding of viral peptides is a key step in the presentation of peptide-MHC complexes which activate the T-cell receptor and the cytotoxic T-cell response.

Methods: Using global HAdV genomic data, we predicted MHC-peptide binding within the hexon and penton proteins of F40 and F41. We focused on MHC Class I alleles common in the UK and Kenya and identified predicted MHC Class I epitopes. Eight predicted epitope pairs from the F41 hexon were synthesized as 15-mer peptides, comparing the wildtype (1970 F41 reference) to the variant (2019-22) sequences. Cellular interferon gamma (IFN-γ) responses to these epitopes were measured in healthy donors using FluoroSpot assays.

Results: We identified multiple predicted Class I epitopes shared between HAdV species C and F, but also unique to species F, and epitopes unique to each genotype. We show that IFN-γ and IL-2 (interleukin 2) peripheral blood mononuclear cell (PBMC) responses to HAdV-F are ubiquitous among healthy adult donors from Cambridge, UK. Among predicted Class I epitopes within the F41 hexon, 11/16 peptides elicited donor positive IFN-γ responses from healthy donor PBMC (at least one epitope from seven out of eight peptide pairs).

Conclusions: The hexon and penton proteins of HAdV-F-40 and F41 are predicted to contain a number of genotype-specific, but conserved, Class I epitopes which could be used to inform future vaccine design. Using the hexon of F41 as a case study, we show that predicted T-cell epitopes in emergent strains are able to elicit an inflammatory cytokine response from healthy donor PBMC. The role of T-cell recognition in driving enteric adenovirus evolution deserves further consideration.

Comparative complete genome analyses were conducted on 173 field outbreak strains of foot-and-mouth disease virus (FMDV) serotype A, collected from various regions worldwide, including strains that have circulated in India in recent years. Phylogenetic analyses revealed that the majority of isolates included in this study belonged to the Asia (n = 108), followed by EURO-SA (n = 41) and Africa (n = 24) topotypes. The mean rate of evolutionary change in FMDV serotype A was estimated to be 2.369 × 10^-3 substitutions/site/year for the Open Reading Frame (ORF). Faster substitution rates in the Asia topotype suggests heightened selective pressures, likely driven by pre-existing host immune responses due to prior infections or vaccination. The periodic emergence and subsequent dominance of notable genotypes or lineages within the Asia topotype such as genotype 18 (ASIA/VII), genotype 20 (Sea-97), and genotype 26 (Iran-05) underscore the ongoing diversification, adaptation, and selection of the virus in the field across Asia. Monophyletic clustering within the Asia and Africa topotypes suggests region-specific evolutionary trajectories, while the diversity observed within EURO-SA indicates an older and more genetically varied lineage pattern. The presence of amino acid insertions and deletions in some of the isolates points to potential hotspots for genetic change, particularly in regions such as L, VP1, and 3A, reflecting high genetic volatility. Positive selection across the protein-coding regions excluding VP4 and 2A highlights the virus's adaptive potential, likely contributing to immune evasion, host adaptation, and enhanced fitness for replication and transmission. Evidence of recombination events, particularly in five isolates with spatio-temporal overlaps, indicates dynamic viral evolution potentially favourable for emergence of new variants. These findings are crucial for understanding foot-and-mouth disease (FMD) epidemiology and may have implications for global FMD control strategies.

Background: Human immunodeficiency virus type 1 (HIV-1) is one of the fastest-evolving human pathogens. Understanding HIV-1 transmission, within-host adaptation, and evolutionary dynamics is pivotal for development of interventions and vaccines. HIV-1 infection is generally caused by a single transmitted founder virus (TFV), and TFV sequences are typically obtained using single genome amplification (SGA). However, suboptimal sample quality can cause sequencing failures, representing considerable losses considering the scarcity of acute HIV-1 infection (AHI) samples. Sequencing failures may be mitigated by molecular cloning (MC), which can be less vulnerable to sample quality but more susceptible to polymerase chain reaction (PCR) errors. Here, we explore the feasibility of supplementing SGA with MC data using samples from clinical and research cohorts to determine whether sequence diversity and evolutionary rate estimates are comparable between the techniques.

Methods: Plasma samples were selected from participants with documented AHI from an East African research cohort (the International AIDS Vaccine Initiative, 2006-2011) and a clinical cohort from Sweden (1983-2011). SGA and MC sequencing were done on the HIV-1 env V1-V3 region (~940 base pairs). Within-host sequence diversity was determined from maximum likelihood phylogenetic trees, and evolutionary rate by Bayesian phylogenetic analysis. Highlighter plots, Hamming distances, and assessment of star phylogenies were used to quantify TFVs.

Results: One hundred participants (median age 30.3 years, 15% female), contributing 350 samples from four longitudinal time points, 10-540 days post-infection, met the inclusion criteria. SGA succeeded on 90% of research cohort and 48% of clinical cohort samples. Comparative analysis of linked SGA and MC data from 10 samples indicated that approximately eight sequences were necessary for diversity estimates. Consistently higher sequence diversity was observed among MC relative to SGA sequences (median [IQR]: 0.009 [0.003, 0.015] and 0.004 [0.001, 0.012] substitutions/site, P = .002), whereas evolutionary rates were comparable between the two methods (0.016 [0.012, 0.019] and 0.011 [0.008, 0.020] substitutions/site/year, P = .232). Five participants with samples obtained within 45 days post-infection were eligible for TFV quantification, and all found to have one TFV using both techniques.

Conclusion: MC data is a suitable supplement for SGA-based HIV-1 studies to preserve the value of precious samples for analysis of evolutionary rate, but not for sequence diversity.

Human noroviruses are genetically diverse and over 30 different genotypes, mainly from genogroups GI and GII, are known to infect humans. Understanding of human norovirus diversity is still incomplete, and this large genetic diversity across and even within genotypes raises important questions about the origins of this diversity and how it is shaped within and between infected individuals. To gain insight into the origin of this genetic diversity, we analysed intra-host norovirus evolution from individuals experimentally infected with the prototype norovirus strain, Norwalk virus (GI.1[P1]). We investigated intra-host viral dynamics, the impact of antibody responses on intra-host viral evolution, inoculum-to-host viral evolution, and whether detected intra-host mutations have evidence of global (population-level) circulation. Notably, most intra-inoculum mutations detected in two GI.1 norovirus inoculum pools were not detected in individuals challenged with those inocula. Likewise, the majority of all intra-host mutations detected in challenged individuals were not detected in the inoculum and thus likely arose de novo within these individuals. Most of them were detected only once during shedding and have not been circulating at appreciable levels at the population level. Structural analyses confirmed that there was no significant difference in the distribution of intra-host mutations on the proteins among specimens with or without positive serum antibody responses. Our analyses suggest that stochastic processes, rather than host immune pressure, govern patterns of intra-host viral diversity in experimental, acute human norovirus infections. They further suggest that strong fitness constraints act to purify the majority of mutations during infection. Further studies that investigate structural and chemical constraints of this virus as well as fitness effects of mutations across the viral genome could help in our understanding of norovirus evolution.