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Evolution of drug resistance in multiple distinct lineages of H5N1 avian influenza
Title: Evolution of drug resistance in multiple distinct lineages of H5N1 avian influenza
Date: October 13, 2008
Author: Andrew W. Hill et al.
Institution: Infection, Genetics and Evolution
Bibliographic Entry: Hill, Andrew W. et al. “Evolution of drug resistance in multiple distinct lineages of H5N1 avian influenza.” October 13, 2008. Infection, Genetics and Evolution Volume 9, Issue 2, March 2009, Pages 169-178. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W8B-4TT9GK9-1&_user=952835&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000049198&_version=1&_urlVersion=0&_userid=952835&md5=403ebf789b326e4737f5e43465fd7e78 (Accessed April 29, 2009)
Electronic Link: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W8B-4TT9GK9-1&_user=952835&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000049198&_version=1&_urlVersion=0&_userid=952835&md5=403ebf789b326e4737f5e43465fd7e78
Key Words: H5N1, avian influenza, bird flu, Tamiflu, adamantine, pandemic influenza, public health preparedness, oseltamivir
Summary of Key Points, Issues, Conclusions: Some predict that influenza A H5N1 will be the cause of a pandemic among humans. In preparation for such an event, many governments and organizations have stockpiled antiviral drugs such as oseltamivir (Tamiflu®). However, it is known that multiple lineages of H5N1 are already resistant to another class of drugs, adamantane derivatives, and a few lineages are resistant to oseltamivir. The evolutionary history of the mutations that confer drug resistance in the H5N1 population continues to be misunderstood. In order to address these discrepancies, phylogenetic analyses of 676 genomic sequences of H5N1 were conducted and the resulting hypotheses were used as a basis for asking 3 molecular evolutionary questions:
(1) Have drug-resistant genotypes arisen in distinct lineages of H5N1 through point mutation or through reassortment?
(2) Is there evidence for positive selection on the codons that lead to drug resistance?
(3) Is there evidence for covariation between positions in the genome that confer resistance to drugs and other positions, unrelated to drug resistance, that may be under selection for other phenotypes?
An examination of how drug-resistant lineages proliferate across the landscape was assessed by projecting or phylogenetic analysis onto a virtual globe. The results for H5N1 show that in most cases drug resistance has arisen by independent point mutations rather than reassortment or covariation. Furthermore, it was discovered that some codons that mediate resistance to adamantane derivatives are under positive selection, but did not find positive selection on codons that mediate resistance to oseltamivir. Collectively, phylogenetic methods, molecular evolutionary analyses, and geographic visualization provide a framework for analysis of globally distributed genomic data that can be used to monitor the evolution of drug resistance.
Name of Researcher: Ashanti Z. Corey
Institution: Integrative Center for Homeland Security, Texas A&M University
Date Posted: April 30, 2009