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Reassortment Network of Influenza A Virus.

ABSTRACT: Influenza A virus (IAV) genomes are composed of eight single-stranded RNA segments. Genetic exchange through reassortment of the segmented genomes often endows IAVs with new genetic characteristics, which may affect transmissibility and pathogenicity of the viruses. However, a comprehensive understanding of the reassortment history of IAVs remains lacking. To this end, we assembled 40,296 whole-genome sequences of IAVs for analysis. Using a new clustering method based on Mean Pairwise Distances in the phylogenetic trees, we classified each segment of IAVs into clades. Correspondingly, reassortment events among IAVs were detected by checking the segment clade compositions of related genomes under specific environment factors and time period. We systematically identified 1,927 possible reassortment events of IAVs and constructed their reassortment network. Interestingly, minimum spanning tree of the reassortment network reproved that swine act as an intermediate host in the reassortment history of IAVs between avian species and humans. Moreover, reassortment patterns among related subtypes constructed in this study are consistent with previous studies. Taken together, our genome-wide reassortment analysis of all the IAVs offers an overview of the leaping evolution of the virus and a comprehensive network representing the relationships of IAVs.

SUBMITTER: Gong X

PROVIDER: S-EPMC8716808 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Reassortment Network of Influenza A Virus.

Gong Xingfei X Hu Mingda M Chen Wei W Yang Haoyi H Wang Boqian B Yue Junjie J Jin Yuan Y Liang Long L Ren Hongguang H

Frontiers in microbiology 20211216

Influenza A virus (IAV) genomes are composed of eight single-stranded RNA segments. Genetic exchange through reassortment of the segmented genomes often endows IAVs with new genetic characteristics, which may affect transmissibility and pathogenicity of the viruses. However, a comprehensive understanding of the reassortment history of IAVs remains lacking. To this end, we assembled 40,296 whole-genome sequences of IAVs for analysis. Using a new clustering method based on Mean Pairwise Distances ...[more]

PMID: 34975817

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Project description:RNA viruses can exchange genetic material during coinfection, an interaction that creates novel strains with implications for viral evolution and public health. Influenza A viral genetic exchange can occur when genome segments from distinct strains reassort in coinfected cells. Predicting potential genomic reassortment between influenza strains has been a long-standing goal. Experimental coinfection studies have shed light on factors that limit or promote reassortment. However, determining the reassortment potential between diverse Influenza A strains has remained elusive. To address this challenge, we developed a high throughput genotyping approach to quantify reassortment among a diverse panel of human influenza virus strains encompassing two pandemics (swine and avian origin), three specific epidemics, and both circulating human subtypes A/H1N1 and A/H3N2. We found that reassortment frequency (the proportion of reassortants generated) is an emergent property of specific pairs of strains where strain identity is a predictor of reassortment frequency. We detect little evidence that antigenic subtype drives reassortment as intersubtype (H1N1xH3N2) and intrasubtype reassortment frequencies were, on average, similar. Instead, our data suggest that certain strains bias the reassortment frequency up or down, independently of the coinfecting partner. We observe that viral productivity is also an emergent property of coinfections, but uncorrelated to reassortment frequency; thus viral productivity is a separate factor affecting the total number of reassortants produced. Assortment of individual segments among progeny and pairwise segment combinations within progeny generally favored homologous combinations. These outcomes were not related to strain similarity or shared subtype but reassortment frequency was closely correlated to the proportion of both unique genotypes and of progeny with heterologous pairwise segment combinations. We provide experimental evidence that viral genetic exchange is potentially an individual social trait subject to natural selection, which implies the propensity for reassortment is not evenly shared among strains. This study highlights the need for research incorporating diverse strains to discover the traits that shift the reassortment potential to realize the goal of predicting influenza virus evolution resulting from segment exchange.

Project description:BackgroundThe segmented RNA genome of avian Influenza viruses (AIV) allows genetic reassortment between co-infecting viruses, providing an evolutionary pathway to generate genetic innovation. The genetic diversity (16 haemagglutinin and 9 neuraminidase subtypes) of AIV indicates an extensive reservoir of influenza viruses exists in bird populations, but how frequently subtypes reassort with each other is still unknown. Here we quantify the reassortment patterns among subtypes in the Eurasian avian viral pool by reconstructing the ancestral states of the subtypes as discrete states on time-scaled phylogenies with respect to the internal protein coding segments. We further analyzed how host species, the inferred evolutionary rates and the dN/dS ratio varied among segments and between discrete subtypes, and whether these factors may be associated with inter-subtype reassortment rate.ResultsThe general patterns of reassortment are similar among five internal segments with the exception of segment 8, encoding the Non-Structural genes, which has a more divergent phylogeny. However, significant variation in rates between subtypes was observed. In particular, hemagglutinin-encoding segments of subtypes H5 to H9 reassort at a lower rate compared to those of H1 to H4, and Neuraminidase-encoding segments of subtypes N1 and N2 reassort less frequently than N3 to N9. Both host species and dN/dS ratio were significantly associated with reassortment rate, while evolutionary rate was not associated. The dN/dS ratio was negatively correlated with reassortment rate, as was the number of negatively selected sites for all segments.ConclusionsThese results indicate that overall selective constraint and host species are both associated with reassortment rate. These results together identify the wild bird population as the major source of new reassortants, rather than domestic poultry. The lower reassortment rates observed for H5N1 and H9N2 may be explained by the large proportion of strains derived from domestic poultry populations. In contrast, the higher rates observed in the H1N1, H3N8 and H4N6 subtypes could be due to their primary origin as infections of wild birds with multiple low pathogenicity strains in the large avian reservoir.

Project description:H9N2 Avian influenza virus (AIV) is regarded as a principal donor of viral genes through reassortment to co-circulating influenza viruses that can result in zoonotic reassortants. Whether H9N2 virus can maintain sustained evolutionary impact on such reassortants is unclear. Since 2013, avian H7N9 virus had caused five sequential human epidemics in China; the fifth wave in 2016-2017 was by far the largest but the mechanistic explanation behind the scale of infection is not clear. Here, we found that, just prior to the fifth H7N9 virus epidemic, H9N2 viruses had phylogenetically mutated into new sub-clades, changed antigenicity and increased its prevalence in chickens vaccinated with existing H9N2 vaccines. In turn, the new H9N2 virus sub-clades of PB2 and PA genes, housing mammalian adaptive mutations, were reassorted into co-circulating H7N9 virus to create a novel dominant H7N9 virus genotype that was responsible for the fifth H7N9 virus epidemic. H9N2-derived PB2 and PA genes in H7N9 virus conferred enhanced polymerase activity in human cells at 33°C and 37°C, and increased viral replication in the upper and lower respiratory tracts of infected mice which could account for the sharp increase in human cases of H7N9 virus infection in the 2016-2017 epidemic. The role of H9N2 virus in the continual mutation of H7N9 virus highlights the public health significance of H9N2 virus in the generation of variant reassortants of increasing zoonotic potential.IMPORTANCEAvian H9N2 influenza virus, although primarily restricted to chicken populations, is a major threat to human public health by acting as a donor of variant viral genes through reassortment to co-circulating influenza viruses. We established that the high prevalence of evolving H9N2 virus in vaccinated flocks played a key role, as donor of new sub-clade PB2 and PA genes in the generation of a dominant H7N9 virus genotype (G72) with enhanced infectivity in humans during the 2016-2017 N7N9 virus epidemic. Our findings emphasize that the ongoing evolution of prevalent H9N2 virus in chickens is an important source, via reassortment, of mammalian adaptive genes for other influenza virus subtypes. Thus, close monitoring of prevalence and variants of H9N2 virus in chicken flocks is necessary in the detection of zoonotic mutations.

Dataset Information

Reassortment Network of Influenza A Virus.

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Reassortment Network of Influenza A Virus.

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