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Domain analysis of symbionts and hosts (DASH) in a genome-wide survey of pathogenic human viruses.

ABSTRACT: In the coevolution of viruses and their hosts, viruses often capture host genes, gaining advantageous functions (e.g. immune system control). Identifying functional similarities shared by viruses and their hosts can help decipher mechanisms of pathogenesis and accelerate virus-targeted drug and vaccine development. Cellular homologs in viruses are usually documented using pairwise-sequence comparison methods. Yet, pairwise-sequence searches have limited sensitivity resulting in poor identification of divergent homologies.Methods based on profiles from multiple sequences provide a more sensitive alternative to identify similarities in host-pathogen systems. The present work describes a profile-based bioinformatics pipeline that we call the Domain Analysis of Symbionts and Hosts (DASH). DASH provides a web platform for the functional analysis of viral and host genomes. This study uses Human Herpesvirus 8 (HHV-8) as a model to validate the methodology. Our results indicate that HHV-8 shares at least 29% of its genes with humans (fourteen immunomodulatory and ten metabolic genes). DASH also suggests functions for fifty-one additional HHV-8 structural and metabolic proteins. We also perform two other comparative genomics studies of human viruses: (1) a broad survey of eleven viruses of disparate sizes and transcription strategies; and (2) a closer examination of forty-one viruses of the order Mononegavirales. In the survey, DASH detects human homologs in 4/5 DNA viruses. None of the non-retro-transcribing RNA viruses in the survey showed evidence of homology to humans. The order Mononegavirales are also non-retro-transcribing RNA viruses, however, and DASH found homology in 39/41 of them. Mononegaviruses display larger fractions of human similarities (up to 75%) than any of the other RNA or DNA viruses (up to 55% and 29% respectively).We conclude that gene sharing probably occurs between humans and both DNA and RNA viruses, in viral genomes of differing sizes, regardless of transcription strategies. Our method (DASH) simultaneously analyzes the genomes of two interacting species thereby mining functional information to identify shared as well as exclusive domains to each organism. Our results validate our approach, showing that DASH has potential as a pipeline for making therapeutic discoveries in other host-symbiont systems. DASH results are available at http://tinyurl.com/spouge-dash.

SUBMITTER: Gonzalez MW

PROVIDER: S-EPMC3672079 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Domain analysis of symbionts and hosts (DASH) in a genome-wide survey of pathogenic human viruses.

Gonzalez Mileidy W MW Spouge John L JL

BMC research notes 20130524

<h4>Background</h4>In the coevolution of viruses and their hosts, viruses often capture host genes, gaining advantageous functions (e.g. immune system control). Identifying functional similarities shared by viruses and their hosts can help decipher mechanisms of pathogenesis and accelerate virus-targeted drug and vaccine development. Cellular homologs in viruses are usually documented using pairwise-sequence comparison methods. Yet, pairwise-sequence searches have limited sensitivity resulting i ...[more]

PMID: 23706066

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Project description:Influenza B virus (IBV) undergoes seasonal antigenic drift more slowly than influenza A virus, but the reasons for this difference are unclear. While the evolutionary dynamics of influenza viruses play out globally, they are fundamentally driven by mutation, reassortment, drift, and selection at the level of individual hosts. These processes have recently been described for influenza A virus, but little is known about the evolutionary dynamics of IBV during individual infections and transmission events. Here, we define the within-host evolutionary dynamics of IBV by sequencing virus populations from naturally infected individuals enrolled in a prospective, community-based cohort over 8,176 person-seasons of observation. Through analysis of high depth-of-coverage sequencing data from samples from 91 individuals with influenza B, we find that IBV accumulates lower genetic diversity than previously observed for influenza A virus during acute infections. Consistent with studies of influenza A viruses, the within-host evolution of IBVs is characterized by purifying selection and the general absence of widespread positive selection of within-host variants. Analysis of shared genetic diversity across 15 sequence-validated transmission pairs suggests that IBV experiences a tight transmission bottleneck similar to that of influenza A virus. These patterns of local-scale evolution are consistent with the lower global evolutionary rate of IBV.IMPORTANCE The evolution of influenza virus is a significant public health problem and necessitates the annual evaluation of influenza vaccine formulation to keep pace with viral escape from herd immunity. Influenza B virus is a serious health concern for children, in particular, yet remains understudied compared to influenza A virus. Influenza B virus evolves more slowly than influenza A virus, but the factors underlying this are not completely understood. We studied how the within-host diversity of influenza B virus relates to its global evolution by sequencing viruses from a community-based cohort. We found that influenza B virus populations have lower within-host genetic diversity than influenza A virus and experience a tight genetic bottleneck during transmission. Our work provides insights into the varying dynamics of influenza viruses in human infection.

Dataset Information

Domain analysis of symbionts and hosts (DASH) in a genome-wide survey of pathogenic human viruses.

Publications

Domain analysis of symbionts and hosts (DASH) in a genome-wide survey of pathogenic human viruses.

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