Virus Evolution最新文献

Cancer-inducing viruses (oncogenic viruses) are linked to over 10% of cancer cases. Although the molecular details of viral oncogenesis are well-documented, the evolutionary mechanisms by which viruses have acquired oncogenic properties remain poorly understood. Here, we investigate the evolutionary conditions affecting viral oncogenicity across both within- and between-host scales using mathematical models of oncovirus-immune system interactions, conceptualized as an extended shared enemy-victim relationship. We begin by examining how oncogenic traits impact within-host viral dynamics, focusing on the transformation rate of infected cells into pre-cancerous states and the pre-cancerous cell proliferation rate. In various scenarios reflecting different within-host conditions, we then identify the transformation and proliferation rates that maximize within- and between-host viral fitness. We find that the transformation rate maximizing the viral load depends on the viral production rate, immunogenicity, and the immune-mediated elimination rate of pre-cancerous cells. We also identify conditions under which an intermediate proliferation rate minimizes within- and between-host viral fitness: in that scenario, a lower or higher proliferation rate leads to a higher viral load, providing a possible explanation for the diversity of oncogenic viruses. The analyses presented here provide insights into the evolutionary drivers affecting viral oncogenicity and highlight the complexity of oncogenic virus-immune system interactions.

Shrews are primary hosts for mammalian hantaviruses and are thus considered to be important reservoirs for viruses, similar to rodents and bats. To explore the diversity of hantaviruses in Swedish common shrews (Sorex araneus), we investigated lung tissue from shrews collected between 2015 and 2017. The collection took place at three separate locations in south-central Sweden. Screening for hantaviruses was performed using two different approaches. (i) A total of 113 common shrews were investigated for hantaviruses by a pan-hantavirus L-gene reverse transcriptase PCR, and Sanger sequencing was performed on the 13 positive samples. (ii) In addition, 88 RNA samples were pooled into eight libraries subjected to RNA sequencing. The RNA sequencing data analysis, which focused specifically on identifying hantaviruses, revealed two divergent hantaviruses: the complete genome of an Altai virus (ALTV) and the partial genome of the Seewis virus. Evolutionary analysis revealed that Swedish ALTVs are closely related to Russian ALTVs but distinct from Finnish strains. On the contrary, the Swedish Seewis virus shares closer ancestry with Finnish Seewis virus strains. Given that these viruses were identified in several pools, Seewis virus and ALTV are likely circulating in Swedish common shrews. Supported by earlier studies, common shrews are probably a natural host for at least these two distinct hantaviruses.

Epidemics are often initiated by emerging and re-emerging infectious diseases caused by viruses of animal origin. It is thus important to identify the reservoirs of potentially zoonotic viruses and understand the dynamics of their host shifts. The flu viruses belong to the virus family Orthomyxoviridae, which also contains Isavirus, Quaranjavirus, and Thogotovirus. Many members of this virus family are known to be pathogenic to humans. For initial surveillance of animal-originated or zoonotic Orthomyxoviridae, unclassified viruses were screened by the use of high-throughput transcriptomes as a data source because of their wide species and lineage coverage. We identified 96 novel or unclassified Orthomyxoviridae members with the discovery of three new lineages of the virus, possibly new genera, one sister to Influenza + Thogotovirus, one to Influenza + Thogotovirus + Quaranjavirus, and another one to all orthomyxoviruses except Isavirus. Throughout the evolution of Orthomyxoviridae, there might be multiple host-shifting incidences, shifting between six different animal host phyla. The most common host shifts seemed to be between Arthropoda and Chordata; however, further evidence would be needed to fully support this statement. Nonetheless, Orthomyxoviridae viruses can infect a wide range of animal phyla, while some members hold a higher risk of shifting back to Chordates and humans that warrants surveillance.

Rodents and other non-volant small mammals (like shrews) maintain major ecological and epidemiological roles as reservoirs of zoonotic pathogens. Their presence within human-modified landscapes and interfaces with people, wildlife, and livestock create frequent opportunities for viral spillover. Despite this, the pathogen diversity and true risk of viral transmission are poorly understood by these hosts in Africa. Here, we explored the diversity and host association of paramyxoviruses and coronaviruses in non-volant small mammals from South Africa through longitudinal and opportunistic sample collection and molecular detection of viral RNA and host genetic barcoding. A high diversity of viruses was identified, with prevalences of 11.9% and 1.79% for paramyxoviruses and coronaviruses, respectively. Five instances of coinfections involving multiple paramyxoviruses and a coronavirus were detected, as well as nine Bayesian-supported paramyxovirus host genus, subfamily, and family switching, signifying frequent unrestrained viral sharing. Though the zoonotic potential of these identified viruses is unknown, the frequency of host switching suggests that these viruses may be more prone to adaptation to new host species or utilize highly conserved entry mechanisms. This highlights the risks for potential cross-species transmission events to livestock, domestic animals, and people, warranting continued surveillance.

Viruses impose a substantial disease burden on dogs, and the close relationship between dogs and humans may facilitate zoonotic disease emergence. Australia's geographic isolation, strict biosecurity measures, and native dingo populations present a unique model for understanding the spread and evolution of canine viruses. However, aside from a few well-characterized pathogens, genomic data are scarce for many common dog viruses, limiting our understanding of their evolution and disease ecology. Using a metatranscriptomic approach, we identified the viruses in dogs and dingoes from various geographical locations across mainland Australia and sample types, revealing 86 vertebrate-associated viruses belonging to 16 distinct species, including a new vesivirus-like species. Many of the viruses identified here have not previously been sequenced in Australia. We identified important dog pathogens associated with canine infectious respiratory disease syndrome-such as canine pneumovirus, canine herpesvirus, and canine respiratory coronavirus-and gastroenteritis, including canine parvovirus, canine coronavirus, and rotavirus A. The sequences of Australian canine viruses often occupied multiple distinct clades phylogenetically and had little geographic structure, suggesting multiple virus introductions and subsequent spread across the country. Notably, we identified the first RNA virus-rotavirus A-in a dingo. This virus was phylogenetically distinct from dog-associated rotavirus A sequences and more closely related to viruses found in humans and bats, indicative of the past cross-species transmission of a reassortant virus into dingoes, and shows dingoes and domestic dogs may have distinct viromes. Our findings expand the knowledge of viral diversity in Australian canines, improving our understanding of viral movement into and within Australia, as well as the potential zoonotic risks associated with dogs and dingoes.

Continuous phylogeographic inference is a popular method to estimate parameters of the dispersal process and to reconstruct the spatial location of ancestors of extant populations from samples viral of genome sequences. However, these models typically ignore that replication and population growth are tightly coupled to spatial location: populations expand in areas with abundant susceptible hosts and contract in regions with limited resources. Here, I first investigate the sampling consistency of popular summary statistics of dispersal and show that estimators of 'lineage velocities' are ill-defined. I then use simulations to investigate how local density regulation or shifting habitats perturb phylogeographic inference in continuous space and show that these can result in biassed and overconfident estimates of ancestral locations and dispersal parameters. These, sometimes dramatic, distortions depend in complicated ways on the past dynamics of habitats and underlying population dynamics and dispersal processes. Consequently, the validity of continuous phylogeographic inferences is hard to assess and confidence can be much lower than suggested by the inferred posterior distributions, in particular when involving poorly sampled locations or extrapolations far into the past.

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.