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The origin and global emergence of adamantane resistant A/H3N2 influenza viruses

Martha I Nelson1, Lone Simonsen, Cécile Viboud

  • 1Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA. nelsonma@mail.nih.gov

Virology
|April 28, 2009
PubMed

Insights

Most adamantane-resistant A/H3N2 influenza viruses globally originated from a single 2003 introduction in Hong Kong. This highlights Southeast Asia as a key source for global influenza virus evolution and spread.

Area of Science:

  • Virology
  • Molecular Epidemiology
  • Antimicrobial Resistance

Background:

  • High-level resistance (>90%) to adamantane antivirals in human A/H3N2 influenza viruses is prevalent in the US and Asia.
  • Adamantane resistance is linked to the S31N mutation in the M2 protein, which spread globally after a 2005 reassortment event.
  • The precise origin of S31N-mutated A/H3N2 viruses, especially in Southeast Asia, remains unclear.

Purpose of the Study:

  • To investigate the origin and phylogenetic history of adamantane-resistant A/H3N2 influenza viruses.
  • To characterize the dissemination of the S31N M2 mutation in influenza A/H3N2 viruses globally.
  • To explore the role of Southeast Asia in the ecology and spread of influenza viruses.

Main Methods:

  • Phylogenetic analysis of hemagglutinin (HA), neuraminidase (NA), and M1/M2 segments.
  • Analysis of viral isolates collected between 1997 and 2007 from New York, New Zealand, Australia, and Hong Kong.
  • Tracking the emergence and spread of the S31N mutation in the M2 protein.

Main Results:

  • The S31N mutation was introduced independently at least 11 times.
  • The majority of currently circulating resistant viruses trace back to a single introduction detected in Hong Kong in summer 2003.
  • Resistant viruses persisted in Hong Kong (2003-2005), acquired a new HA via reassortment in early 2005, and then spread globally.
  • Hong Kong served as the origin for the dominant global lineage of resistant A/H3N2 viruses.

Conclusions:

  • Southeast Asia, specifically Hong Kong, is a critical origin point for the global spread of adamantane-resistant A/H3N2 influenza.
  • The findings support a source-sink model of influenza virus ecology, where Southeast Asia repeatedly seeds epidemics in temperate regions.
  • Understanding viral origins is crucial for predicting and controlling influenza pandemics.

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