Selection for resistance to oseltamivir in seasonal and pandemic H1N1 influenza and widespread co-circulation of the lineages.
BACKGROUND
In Spring 2009, a novel reassortant strain of H1N1 influenza A emerged as a lineage distinct from seasonal H1N1. On June 11, the World Heath Organization declared a pandemic - the first since 1968. There are currently two main branches of H1N1 circulating in humans, a seasonal branch and a pandemic branch. The primary treatment method for pandemic and seasonal H1N1 is the antiviral drug Tamiflu (oseltamivir). Although many seasonal H1N1 strains around the world are resistant to oseltamivir, initially, pandemic H1N1 strains have been susceptible to oseltamivir. As of February 3, 2010, there have been reports of resistance to oseltamivir in 225 cases of H1N1 pandemic influenza. The evolution of resistance to oseltamivir in pandemic H1N1 could be due to point mutations in the neuraminidase or a reassortment event between seasonal H1N1 and pandemic H1N1 viruses that provide a neuraminidase carrying an oseltamivir-resistant genotype to pandemic H1N1.


RESULTS
Using phylogenetic analysis of neuraminidase sequences, we show that both seasonal and pandemic lineages of H1N1 are evolving to direct selective pressure for resistance to oseltamivir. Moreover, seasonal lineages of H1N1 that are resistant to oseltamivir co-circulate with pandemic H1N1 throughout the globe. By combining phylogenetic and geographic data we have thus far identified 53 areas of co-circulation where reassortment can occur. At our website POINTMAP, http://pointmap.osu.edu we make available a visualization and an application for updating these results as more data are released.


CONCLUSIONS
As oseltamivir is a keystone of preparedness and treatment for pandemic H1N1, the potential for resistance to oseltamivir is an ongoing concern. Reassortment and, more likely, point mutation have the potential to create a strain of pandemic H1N1 against which we have a reduced number of treatment options.
Janies
Daniel A
DA
Department of Biomedical Informatics, The Ohio State University, College of Medicine, Columbus, OH 43210, USA. Daniel.Janies@osumc.edu
Voronkin
Igor O
IO
Studer
Jonathon
J
Hardman
Jori
J
Alexandrov
Boyan B
BB
Treseder
Travis W
TW
Valson
Chandni
C
D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016000:Cluster Analysis; D021821:Communicable Diseases, Emerging / Q000453:epidemiology / Q000235:genetics / Q000821:virology; D004196:Disease Outbreaks; D024882:Drug Resistance, Viral; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology / Q000235:genetics*; D007251:Influenza, Human / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000235:genetics; D053139:Oseltamivir / Q000494:pharmacology / Q000627:therapeutic use*; D010802:Phylogeny
D000998:Antiviral Agents; D053139:Oseltamivir; D009439:Neuraminidase