Virus Evolution最新文献

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.

Influenza A viruses (IAVs) in swine have zoonotic potential and pose a continuous threat of causing human pandemics, as demonstrated by the H1N1 pandemic in 2009. Despite increased genomic surveillance, we have limited knowledge of the IAV evolutionary dynamics leading to such zoonotic events and no clear understanding of genetic markers associated with interspecies transmission of IAV between humans and swine. To explore this, we analysed a comprehensive publicly available whole-genome dataset of human and swine IAV sequences. We conducted phylogenetic analyses and inference of ancestral host and sequence states for each IAV segment to map inferred mutations associated with hypothetical representative transmissions within and between swine and human hosts. We developed a custom python library to combine information from host and ancestral sequence annotated trees and applied statistical models to identify genetic markers associated with intra- or interspecies transmissions between swine and humans. This included analysing mutation rates and the selective pressures acting on the viral proteins following intra- and interspecies transmissions and using a scalable, gradient-boosted decision tree machine learning approach to predict key amino acid positions critical for different transmission types. Our analyses not only indicated complex mutational patterns within and across viral proteins, but also suggested that specific protein regions and amino acid positions of especially several of the internal gene segments were more important for interspecies transmission. Our findings identify potential genetic signatures across the IAV proteins associated with host adaptation and zoonotic potential, offering valuable markers for early-warning genomic surveillance systems to enhance animal health and minimize the potential for zoonotic transmission of IAV.

The incidence of arboviral diseases like dengue, chikungunya, and yellow fever continues to rise in association with the expanding geographic ranges of their vectors, Aedes aegypti and Aedes albopictus. The distribution of these vectors is believed to be driven in part by climate change and increasing urbanization. Arboviruses navigate a wide range of temperatures as they transition from ectothermic vectors (from 15°C to 35°C) to humans (37°C) and back again, but the role that temperature plays in driving the evolution of arboviruses remains largely unknown. Here, we passaged replicate dengue serotype-2 virus populations 10 times at either 26°C (Low) or 37°C (High) in C6/36 Aedes albopictus cells to explore the differences in adaptation to these thermal environments. We then deep-sequenced the resulting passaged dengue virus populations and tested their replicative fitness in an all-cross temperature regime. We also assessed the ability of the passaged viruses to replicate in the insect vector. While viruses from both thermal regimes accumulated substitutions, only those reared in the 37°C treatments exhibited nonsynonymous changes, including several in the E, or envelope protein, and multiple non-structural genes. Passaging at the higher temperature also led to reduced replicative ability at 26°C in both cells and mosquitoes. One of the mutations in the E gene involved the loss of a glycosylation site previously shown to reduce infectivity in the vector. These findings suggest that viruses selected for growth at higher ambient temperatures may experience tradeoffs between thermostability and replication in the vector. Such associations might also have implications for the suitability of virus transmission under a changing climate.

Ticks are important vectors for pathogen transmission, yet studies on the diversity and distribution of viruses carried by ticks in desert regions remain limited. This study investigated the tick virome in desert areas of Xinjiang, China, and identified two tick species, Hyalomma asiaticum and Rhipicephalus turanicus. A total of 30 meta-transcriptome sequencing libraries were constructed from ticks pooled by location, tick species, sex, and host. The proportion of viral reads ranged from 0.004% to 0.165%, and significant differences in viral alpha- and beta-diversity were observed between the two tick species. A total of 125 complete or nearly complete viral genomes were classified into 5 families of positive-sense single-stranded RNA viruses, 6 families of negative-sense single-stranded RNA viruses, and 2 families of double-stranded RNA viruses. Twenty-eight viral species were identified, including 20 known viruses and 8 novel viruses from the genera Orthonairovirus, Quaranjavirus, and Mitovirus, and families Peribunyaviridae and Narnaviridae. Notably, the discovery of Desert orthonairovirus, Desert quaranjavirus, and Desert peribunya-like virus revealed a potential new role for desert ticks as viral vectors. Among the other 25 viruses, 12 were specific to H. asiaticum, and 9 were specific to R. turanicus. This study highlights the diversity of tick-borne viruses in Xinjiang's desert regions, their distribution across different tick species, and underscores the importance of these tick species in pathogen transmission. These findings provide scientific evidence for further research into viral circulation in desert ecosystems and the potential public health threats posed by tick-borne pathogens.

Dengue virus (DENV) is a significant public health concern in Colombia, with increased transmission of DENV type 1 (DENV-1) in the departments of Risaralda and Valle del Cauca in the Central-West region of the country following a large outbreak in 2019. However, little is known about the source, genetic diversity, and evolution of circulating viruses. We obtained serum samples from individuals with acute DENV infection and analysed DENV-1 genetic diversity, phylodynamics, and phylogeography. We found that most viruses belonged to DENV-1 genotype V, and phylogenetic analysis revealed three distinct clades, each of which was most closely related to viruses from neighbouring departments of Colombia sampled over the last 5-10 years. Thus, the 2019 outbreak and subsequent DENV-1 circulation was not due to the introduction of a new lineage to the country but rather reflected local DENV-1 V dispersion and evolution. We identified amino acid positions under positive selection in structural proteins and NS1, which may have a role in immune evasion and pathogenesis. Overall, our analysis of DENV-1 V diversity, evolution, and spread within Colombia highlights the important role of genomic surveillance in understanding virus dynamics during endemic circulation and outbreaks.

N-linked glycosylation of flavivirus envelope proteins is widely viewed as being required for optimal folding, processing and/or transit of envelope proteins, and the assembling virons, through the endoplasmic reticulum (ER) and the Golgi. Zika virus (ZIKV) has a single N-linked envelope glycan located adjacent to the fusion loop. Herein we show that independent serial passage of ZIKV_Natal in Rag1 ^-/- mice for 223 or 386 days generated two unique envelope glycan-deficient mutants, ZIKV-V153D and ZIKV-N154D, respectively. Surprisingly, these mutants grew to titres ∼1 to 2.6 logs higher than the glycosylated parental ZIKV_Natal in Vero E6 cells and human brain organoids. RNA-Seq of infected organoids suggested that this increased replication fitness was associated with upregulation of the unfolded protein response (UPR). Cell death, cellular viral RNA, and viral protein levels were not significantly affected, arguing that these glycan mutants enjoyed faster ER/Golgi folding, processing, assembly, transit, and virion egress, assisted by an upregulated UPR. Thus, ZIKV envelope N-linked glycosylation is not essential for promoting envelope folding, assembly, and transit through the ER/Golgi, since aspartic acid (D) substitutions in the glycosylation motif can achieve this with significantly greater efficiency. Instead, the evolution of glycan mutants in Rag1 ^-/- mice indicates that such envelope glycosylation can have a fitness cost in an environment devoid of virus-specific antibody responses. The V153D and N154D mutations, generated by natural selection in Rag1 ^-/- mice, have to date not been employed in orthoflavivirus envelope glycosylation studies. Instead, genetic engineering has been used to generate mutant viruses that, for instance, contain a N154A substitution. The latter may impart confounding unfavourable properties, such as envelope protein insolubility, that have a detrimental impact on virus replication. The V153D and N154D substitutions may avoid imparting unfavourable properties by preserving the surface negative charge provided by the glycan moiety in the parental ZIKV_Natal envelope protein. In Ifnar1 ^-/- mice ZIKV-V153D and -N154D showed faster viremia onsets, but reduced viremic periods, than the parental ZIKV_Natal, consistent with an established contention that such glycans have evolved to delay neutralizing antibody activity.

Jingmenviruses are a distinct group of flavi-like viruses characterized by a genome consisting of four to five segments. Here, we report the discovery of three novel putative jingmenviruses, identified by mining publicly available metagenomics data from mosquito and arachnid samples. Strikingly, these novel jingmenvirus sequences contain up to six genomic segments, with pairs of homologous segments coding for putative structural proteins. Following this discovery, we found an additional homologous segment for two other jingmenvirus genomes, which had gone unnoticed in the initial publications. The presence of a single version of the segments coding for non-structural proteins suggests that we have indeed identified jingmenviruses with infectious units that contain up to six segments. We compared these novel jingmenvirus sequences to published sequences, in particular the segments with multiple open reading frames (ORFs), and we propose that the putative translation initiation mechanisms involved for these segments are ribosomal frameshift resulting in the fusion of ORFs and leaky scanning for overlapping ORFs. These putative mechanisms, conserved for all jingmenvirus sequences analysed, including in homologous segments, require biological confirmation. We also generated structural models of two putative structural proteins in the duplicated segments, and the corresponding alignments enabled us to confirm or identify the homologous relationship between sequences that shared limited nucleotide or amino acid identity. Altogether, these results highlight the fluid nature of jingmenviruses, which is a hallmark of multipartite viruses. Different combinations of segments packaged in different virus particles could facilitate the acquisition or loss of genomic segments and a segment duplication following genomic drift. Our data therefore contribute to the evidence of the multipartite nature of jingmenviruses and the evolutionary role this organization may play.