Virus Evolution最新文献

The evolution of HIV-1 virulence has significant implications for epidemic control. Recent phylogenomic analyses identified low-prevalence HIV-1 variants exhibiting significant differences in disease progression. We analysed 40 888 partial HIV-1 pol sequences from the UK HIV Drug Resistance Database (UKRDB) across subtypes B, C, A1, and CRF02AG. We identified phylotypes with putative differences in transmission/phylogenetic patterns and assessed their virulence trends using pretreatment viral loads, CD4 cell counts, and four statistical methods. We classified three subtype B phylotypes-PT.B.40.UK, PT.B.69.UK, and PT.B.133.UK -as variants of interest (VOIs) due to significantly higher viral loads and/or accelerated CD4 decline. PT.B.40.UK and PT.B.69.UK exhibited higher viral loads, 4.93 log₁₀ copies/ml (95% CI: 4.73-5.13) and 4.87 (4.65-5.10), representing 0.30-0.36 log₁₀ copies/ml higher than the reference group (4.57; 4.55-4.59). Despite uncertainties in baseline CD4 counts, all three VOIs reached the clinically relevant threshold of 350 CD4 cells/mm³ significantly faster than the reference group (3.5 years, 3.1-3.9 years): 2.3 years (1.0-5.1) for PT.B.40.UK, 2.0 years (10.8 months-4.4 years) for PT.B.69.UK, and 1.8 years (10.8 months-3.6 years) for PT.B.133.UK. These VOIs and their closest relatives have been circulating in the UK for decades with limited international spread and did not exhibit unusually rapid growth rates. Although these findings suggest a heritable high-virulence HIV-1 phenotype, we did not find evidence that convergent genetic polymorphisms or switches in coreceptor usage explained these differences. The small fraction of HIV-1 subtype B variants in the UK evolving towards higher virulence is unlikely to pose a public health concern, given the ongoing decline in new HIV diagnoses following the widespread adoption of pre-exposure prophylaxis and targeted prevention campaigns. However, this study-alongside the detection of the VB variant in the Netherlands-demonstrates that more virulent variants are not rare and can emerge independently in multiple countries. Consequently, HIV-1 genomic surveillance remains crucial to monitor HIV-1 virulence and mitigate its healthcare impact.

Dengue, caused by dengue virus (DENV) 1-4, remains a global public health concern, with Brazil experiencing some of the largest epidemics. The re-emergence of DENV-3 in Brazil between 2023 and 2024 has raised concerns about new outbreaks due to the absence of sustained circulation of this serotype in recent years. This study investigates the dynamics of DENV-3 in Brazil, focusing on the spread of the 3III_B.3.2 lineage within genotype 3III and its introduction routes. We analysed 1536 DENV-3 genomes, including 11 newly generated in this study, all classified as genotype 3III, the dominant DENV-3 genotype in Brazil since 2001. Phylogenetic analysis identified the 3III_B.3.2 lineage in all recent Brazilian cases, with detections also reported in Central America, the USA, and Europe. At least six independent introduction events of this lineage into Brazil were identified, with the Caribbean region as the primary source. The earliest introduction likely occurred in late 2022 in Roraima, followed by introductions in São Paulo, Minas Gerais, and Pará. While one instance of interstate transmission was detected-from São Paulo to Minas Gerais-our findings indicate that external introductions, rather than domestic spread, were the primary drivers of DENV-3 circulation during this period. These results underscore the importance of continued genomic surveillance and coordinated public health strategies to monitor and mitigate future outbreaks.

West Nile Virus (WNV) remains a public health risk across North America due to its capacity for rapid adaptation and evolution. While research in the United States has focused on the WN02 and SW03 mutations, the NY10 genotype, first detected in 2010, has received comparatively little attention. We conducted a phylogenetic and phylodynamic investigation of NY10, revealing its rapid increase in detection frequency and effective population size in the early 2010s. Our analysis suggests that NY10 played an important role in the 2012 WNV outbreak, with an effective population size indicating higher diversity than other lineages during this period. Despite this, NY10 appears geographically restricted, with no detections west of Colorado, indicating that barriers in the southwestern United States may influence its spread. These findings highlight the complex interplay between viral evolution, geography, and the environmental factors that shape WNV epidemiology. The study emphasizes the potential of WNV to generate genotypes with epidemic potential and underscores the importance of integrating genetic data into surveillance and forecasting systems to better predict and manage future outbreaks. Understanding the drivers of WNV's genetic diversity will be crucial for developing more effective public health strategies as the virus continues to evolve.

Coxsackievirus A6 (CVA6) is a major pathogen responsible for numerous outbreaks of hand, foot, and mouth disease (HFMD) worldwide. This study investigates the molecular evolution and recombination of CVA6 in Beijing, China. Full-length sequences of 54 CVA6 from Beijing (2019-2023) were obtained through metagenomic next-generation sequencing and Sanger sequencing. These sequences were compared with representative sequences from GenBank to analyse their phylogenetic characteristics, recombination diversity, and evolutionary dynamics. The 54 CVA6 strains co-circulated with those from multiple provinces in China, as well as from South Korea and Japan. Phylogenetic analysis revealed a novel D3c branch, with the VP1 T283A amino acid mutation identified as a key change in its formation. One sequence belonged to the D3a branch, while 53 sequences belonged to the D3c branch. Recombination analysis identified RF-A (46, 85.1%) and three novel recombinant forms (RFs): RF-Z (1, 1.9%), RF-AA (1, 1.9%), and RF-AB (6, 11.1%). Bayesian phylogenetic analysis estimated that the most recent common ancestor of D3c emerged in August 2013 (95% highest probability density (HPD): May 2012 to September 2014), with recombination events occurring in RF-Z (2017-2019), RF-AA (2019-2023), and RF-AB (2021-2023). In conclusion, we revealed a globally circulating CVA6 D3c branch and identified three novel RFs, providing valuable insights for the intervention and control of HFMD.

The recombinant FY.4 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant was first reported in Kenya in March 2023 and was the dominant circulating variant between April and July 2023. The variant was characterized by two important mutations: Y451H in the receptor-binding domain of the spike protein and P42L in open reading frame 3a. Using phylogenetics and phylodynamic approaches, we investigated the emergence and spread of FY.4 in Kenya and the rest of the world. Our findings suggest FY.4 circulated early in Kenya before its export to North America and Europe. Early circulation of FY.4 in Kenya was predominantly observed in the coastal part of the country, and the estimated time to the most recent common ancestor suggests FY.4 circulated as early as December 2022. The collected genomic and epidemiological data show that the FY.4 variant led to a large local outbreak in Kenya and resulted in localized outbreaks in Europe, North America, and Asia-Pacific. These findings underscore the importance of sustained genomic surveillance, especially in under-sampled regions, in deepening our understanding of the evolution and spread of SARS-CoV-2 variants.

The 2009 H1N1 pandemic (pdm09) lineage is a major component of the H1 influenza A virus (IAV) that causes seasonal outbreaks annually. Since its introduction in the 2009-10 season, this lineage has evolved into distinct, successive clades in humans. Predicting the fitness of influenza clades is essential to forecasting future prevalence, providing a critical opportunity to develop a response to mitigate infection. The relative fitness of pdm09 lineages was retrospectively inferred via relative reproduction rate (RR_e) through RelRe, a programme that implements a renewal equation to estimate the relative difference in reproduction number between cocirculating clades. For this analysis, pdm09 lineage sequences from the USA, collected from 2017 to 2023 in both human and swine hosts, were downloaded from public databases. Clade designations were assigned using Nextclade. Human case count data were divided by each influenza season, and the RR_e was estimated at 3-month intervals. The RR_e was then used to forecast clade frequency 90 days into the future, and the predictions were compared to the historical data. The highest predicted frequency at 90 days corresponded to the most frequently detected lineage in 9 out of 13 predictions (69%). The pdm09 lineage plays an important role at the human-swine influenza interface. Bayesian inference using both human and swine data indicated unequal transmission rates of the pdm09 lineage, with 53-79 noted transmissions from human to swine and 0-2 in reverse using the available genetic data. Metadata analysis revealed that new clades of pdm09 in humans were typically detected in swine as early as ~8-20 months after clade emergence in humans. Understanding RR_e and the fitness of contemporary IAV strains enables the identification of high-risk reverse-zoonotic strains and provides critical time for responding to emergent human clades.

Endogenous retroviruses (ERVs) are remnants of ancestral viral infections in germ cells that constitute a substantial proportion of the mammalian genome and are assumed to provide molecular fossil records of ancient infections. Analysis of these sequences may reveal the mechanisms of virus-host co-evolution, viral endogenization, and extinction. Chimpanzee endogenous retrovirus 1 (CERV1), a gamma retrovirus, is estimated to have circulated within primates for ~10 million years, although it is now apparently extinct. In this study, we aimed to gain an understanding of how the extinct CERV1 was transmitted and endogenized. On the basis of the identification of CERV1 fossils in the primate genome and using the expression-cloning method with the human cDNA library, we found that riboflavin transporter human SLC52A2 served as a receptor for CERV1 entry. The ectopic expression of human and chimpanzee SLC52A2 and its related SLC52A1 in heterogenic cells confers susceptibility to infection by CERV1 and porcine endogenous retrovirus (PERV). Virus interference experiments have shown that CERV1 inhibits infection by PERV and vice versa. This finding indicates that CERV1 and PERV belong to the same virus interference group. CERV1 shows infection in a wide range of human and primate cells. Notably, CERV1 infection is observed in human cell lines that express human SLC52A2 abundantly but hardly express human SLC52A1. Although CERV1 has been established to be present at high copy numbers in the great apes (Pan troglodytes, Pan paniscus, and Gorilla gorilla) and 15 Old World monkey species of the Cercopithecinae and Colobinae subfamilies, it is absent in humans and orangutans. CERV1 gene expression is observed in primates, including chimpanzees, suggesting that CERV1 has co-evolved with its hosts. Our results suggest that ERVs may have conferred resistance to viral infections in a convergent evolutionary manner. These findings are significant not only for advancing the field of paleovirology but also in terms of gaining an understanding of the potential risks of viral infection with respect to xenotransplantation, such as that from pigs to humans.

Bacteriophages (viruses that exclusively infect bacteria) exhibit a continuum of infection mechanisms, including lysis and lysogeny in interactions with bacterial hosts. Recent work has demonstrated the short-term advantages of lysogeny over lysis in conditions of low host availability. Hence, temperate phage which can switch between lytic and lysogenic strategies-both stochastically and responsively-are hypothesized to have an evolutionary advantage in a broad range of conditions. However, the long-term advantages of lysogeny are not well understood, particularly when environmental conditions vary over time. To examine generalized drivers of viral strategies over the short- and long-term, we explore the eco-evolutionary dynamics of temperate viruses in periodic environments with varying levels of host availability and viral mortality. We use a nonlinear system of ordinary differential equations to simulate periodically-forced dynamics that separate a 'within-growth' phase and a 'between-growth' phase, in which a (potentially unequal) fraction of virus particles and lysogens survive. Using this ecological model and invasion analysis, we show and quantify how conflicts can arise between strategies in the short term that may favour lysis and strategies in the long term that may favour lysogeny. In doing so, we identify a wide range of conditions in which temperate strategies can outperform obligately lytic or lysogenic strategies. Finally, we demonstrate that temperate strategies can mitigate against the potential local extinction of viruses in stochastically fluctuating environments, providing further evidence of the eco-evolutionary benefits of being temperate.

The fast evolution of SARS-CoV-2 and other infectious viruses poses a grand challenge to the rapid response in terms of viral tracking, diagnostics, and design and manufacture of monoclonal antibodies (mAbs) and vaccines, which are both time-consuming and costly. This underscores the need for efficient computational approaches. Recent advancements, like topological deep learning (TDL), have introduced powerful tools for forecasting emerging dominant variants, yet they require deep mutational scanning (DMS) of viral surface proteins and associated three-dimensional (3D) protein-protein interaction (PPI) complex structures. We propose an AlphaFold 3 (AF3)-assisted multi-task topological Laplacian (MT-TopLap) strategy to address this need. MT-TopLap combines deep learning with TDA models, such as persistent Laplacians (PL) to extract detailed topological and geometric characteristics of PPIs, thereby enhancing the prediction of DMS and binding free energy (BFE) changes upon virus mutations. Validation with four experimental DMS datasets of SARS-CoV-2 spike receptor-binding domain (RBD) and the human angiotensin-converting enzyme-2 (ACE2) complexes indicates that our AF3-assisted MT-TopLap strategy maintains robust performance, with only an average 1.1% decrease in Pearson correlation coefficients (PCC) and an average 9.3% increase in root mean square errors (RMSE), compared with the use of experimental structures. Additionally, AF3-assisted MT-TopLap achieved a PCC of 0.81 when tested with a SARS-CoV-2 HK.3 variant DMS dataset, confirming its capability to accurately predict BFE changes and adapt to new experimental data, thereby showcasing its potential for rapid and effective response to fast viral evolution.

A viral quasispecies is a genetically diverse population of closely related viral variants that exist in a state of dynamic equilibrium. This diversity, driven by mutations, recombination, and selective pressures, enables viruses to adapt rapidly, affecting pathogenicity and treatment resistance. Quantifying the genetic diversity within viral quasispecies is therefore crucial for understanding viral evolution and for designing effective therapeutic strategies. Entropy is a commonly used metric to measure genetic diversity within such populations; however, traditional entropy calculations often neglect genetic similarities between sequences, which can result in overestimating true diversity. In this study, I compare several widely used diversity indices for quantifying viral quasispecies diversity and introduce a novel similarity-weighted entropy metric that incorporates sequence similarity into entropy calculations. This approach enables a more comprehensive representation of diversity in genetically cohesive viral populations. By applying both conventional and similarity-weighted entropy calculations to hypothetical sequence populations and real viroid and virus quasispecies, I demonstrate that similarity-weighted entropy provides a more comprehensive measure of genetic diversity while maintaining the simplicity of conventional entropy. These findings highlight the value of similarity-weighted entropy in characterizing viral quasispecies and its potential to improve our understanding of viral adaptation and resistance mechanisms.