Identifying changes in selective constraints: host shifts in influenza.

The natural reservoir of Influenza A is waterfowl. Normally, waterfowl viruses are not adapted to infect and spread in the human population. Sometimes, through reassortment or through whole host shift events, genetic material from waterfowl viruses is introduced into the human population causing wor...

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Bibliographic Details
Published in:PLoS Computational Biology
Main Authors: Asif U Tamuri, Mario Dos Reis, Alan J Hay, Richard A Goldstein
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2009
Subjects:
Online Access:https://doi.org/10.1371/journal.pcbi.1000564
https://doaj.org/article/f36c75a4f9d2405096c9b0daf7ee63e8
Description
Summary:The natural reservoir of Influenza A is waterfowl. Normally, waterfowl viruses are not adapted to infect and spread in the human population. Sometimes, through reassortment or through whole host shift events, genetic material from waterfowl viruses is introduced into the human population causing worldwide pandemics. Identifying which mutations allow viruses from avian origin to spread successfully in the human population is of great importance in predicting and controlling influenza pandemics. Here we describe a novel approach to identify such mutations. We use a sitewise non-homogeneous phylogenetic model that explicitly takes into account differences in the equilibrium frequencies of amino acids in different hosts and locations. We identify 172 amino acid sites with strong support and 518 sites with moderate support of different selection constraints in human and avian viruses. The sites that we identify provide an invaluable resource to experimental virologists studying adaptation of avian flu viruses to the human host. Identification of the sequence changes necessary for host shifts would help us predict the pandemic potential of various strains. The method is of broad applicability to investigating changes in selective constraints when the timing of the changes is known.