Dataset Information

Fitness Inference from Short-Read Data: Within-Host Evolution of a Reassortant H5N1 Influenza Virus.

ABSTRACT: We present a method to infer the role of selection acting during the within-host evolution of the influenza virus from short-read genome sequence data. Linkage disequilibrium between loci is accounted for by treating short-read sequences as noisy multilocus emissions from an underlying model of haplotype evolution. A hierarchical model-selection procedure is used to infer the underlying fitness landscape of the virus insofar as that landscape is explored by the viral population. In a first application of our method, we analyze data from an evolutionary experiment describing the growth of a reassortant H5N1 virus in ferrets. Across two sets of replica experiments we infer multiple alleles to be under selection, including variants associated with receptor binding specificity, glycosylation, and with the increased transmissibility of the virus. We identify epistasis as an important component of the within-host fitness landscape, and show that adaptation can proceed through multiple genetic pathways.

SUBMITTER: Illingworth CJ

PROVIDER: S-EPMC4651230 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Fitness Inference from Short-Read Data: Within-Host Evolution of a Reassortant H5N1 Influenza Virus.

Illingworth Christopher J R CJ

Molecular biology and evolution 20150804 11

We present a method to infer the role of selection acting during the within-host evolution of the influenza virus from short-read genome sequence data. Linkage disequilibrium between loci is accounted for by treating short-read sequences as noisy multilocus emissions from an underlying model of haplotype evolution. A hierarchical model-selection procedure is used to infer the underlying fitness landscape of the virus insofar as that landscape is explored by the viral population. In a first appli ...[more]

PMID: 26243288

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Project description:In January and November 2008, outbreaks of avian influenza have been reported in 4 provinces of Thailand. Eight Influenza A H5N1 viruses were recovered from these 2008 AI outbreaks and comprehensively characterized and analyzed for nucleotide identity, genetic relatedness, virulence determinants, and possible sites of reassortment. The results show that the 2008 H5N1 viruses displayed genetic drift characteristics (less than 3% genetic differences), as commonly found in influenza A viruses. Based on phylogenetic analysis, clade 1 viruses in Thailand were divided into 3 distinct branches (subclades 1, 1.1 and 1.2). Six out of 8 H5N1 isolates have been identified as reassorted H5N1 viruses, while other isolates belong to an original H5N1 clade. These viruses have undergone inter-lineage reassortment between subclades 1.1 and 1.2 and thus represent new reassorted 2008 H5N1 viruses. The reassorted viruses have acquired gene segments from H5N1, subclade 1.1 (PA, HA, NP and M) and subclade 1.2 (PB2, PB1, NA and NS) in Thailand. Bootscan analysis of concatenated whole genome sequences of the 2008 H5N1 viruses supported the reassortment sites between subclade 1.1 and 1.2 viruses. Based on estimating of the time of the most recent common ancestors of the 2008 H5N1 viruses, the potential point of genetic reassortment of the viruses could be traced back to 2006. Genetic analysis of the 2008 H5N1 viruses has shown that most virulence determinants in all 8 genes of the viruses have remained unchanged. In summary, two predominant H5N1 lineages were circulating in 2008. The original CUK2-like lineage mainly circulated in central Thailand and the reassorted lineage (subclades 1.1 and 1.2) predominantly circulated in lower-north Thailand. To prevent new reassortment, emphasis should be put on prevention of H5N1 viruses circulating in high risk areas. In addition, surveillance and whole genome sequencing of H5N1 viruses should be routinely performed for monitoring the genetic drift of the virus and new reassorted strains, especially in light of potential reassortment between avian and mammalian H5N1 viruses.

Dataset Information

Fitness Inference from Short-Read Data: Within-Host Evolution of a Reassortant H5N1 Influenza Virus.

Publications

Fitness Inference from Short-Read Data: Within-Host Evolution of a Reassortant H5N1 Influenza Virus.

Similar Datasets

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