JVI Accepts, published online ahead of print on 25 July 2007

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J. Virol. doi:10.1128/JVI.00921-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Persistent Host Markers in Pandemic and H5N1 Influenza Viruses

David B. Finkelstein, Suraj Mukatira, Perdeep K. Mehta, John C. Obenauer, Xiaoping Su, Robert G. Webster, and Clayton W. Naeve^*

Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, 332 North Lauderdale Street Memphis, TN 38105-2794, USA; Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 North Lauderdale Street Memphis, TN 38105-2794, USA; Department of Pathology, University of Tennessee Health Science Center, Memphis, TN 38105, USA

^* To whom correspondence should be addressed. Email: clayton.naeve{at}stjude.org.

Avian influenza viruses have adapted to human hosts causing pandemics in humans. The key host-specific amino acid mutations required for an avian influenza virus to function in humans are unknown. Through multiple sequence alignment and statistical testing of each aligned amino acid we identified markers that discriminate human influenza viruses from avian influenza viruses. We applied strict thresholds to select only markers which are highly preserved in human influenza isolates over time. We found that a subset of these persistent host markers exist in all human pandemic influenza sequences from 1918, 1957 and 1968, while others are acquired as the virus becomes a seasonal influenza. We also show that human H5N1 influenza viruses are significantly more likely to contain the amino acid predominant in human strains for a few persistent host markers when compared to avian H5N1 influenza viruses. This sporadic enrichment of amino acids present in human-hosted viruses may indicate that some H5N1 viruses have made modest adaptations to their new hosts in the recent past. The markers reported here should be useful in monitoring potential pandemic influenza viruses.

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