Key Molecular Factors in Hemagglutinin and PB2 Contribute to Efficient Transmission of the 2009 H1N1 Pandemic Influenza Virus
- 15 September 2012
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 86 (18), 9666-9674
- https://doi.org/10.1128/jvi.00958-12
Abstract
Animal influenza viruses pose a clear threat to public health. Transmissibility among humans is a prerequisite for a novel influenza virus to cause a human pandemic. A novel reassortant swine influenza virus acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. However, the molecular aspects of influenza virus transmission remain poorly understood. Here, we show that an amino acid in hemagglutinin (HA) is important for the 2009 H1N1 influenza pandemic virus (2009/H1N1) to bind to human virus receptors and confer respiratory droplet transmissibility in mammals. We found that the change from glutamine (Q) to arginine (R) at position 226 of HA, which causes a switch in receptor-binding preference from human α-2,6 to avian α-2,3 sialic acid, resulted in a virus incapable of respiratory droplet transmission in guinea pigs and reduced the virus's ability to replicate in the lungs of ferrets. The change from alanine (A) to threonine (T) at position 271 of PB2 also abolished the virus's respiratory droplet transmission in guinea pigs, and this mutation, together with the HA Q226R mutation, abolished the virus's respiratory droplet transmission in ferrets. Furthermore, we found that amino acid 271A of PB2 plays a key role in virus acquisition of the mutation at position 226 of HA that confers human receptor recognition. Our results highlight the importance of both the PB2 and HA genes on the adaptation and transmission of influenza viruses in humans and provide important insights for monitoring and evaluating the pandemic potential of field influenza viruses.Keywords
This publication has 49 references indexed in Scilit:
- Hemagglutinin–neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferretsProceedings of the National Academy of Sciences, 2011
- Continued Evolution of H5N1 Influenza Viruses in Wild Birds, Domestic Poultry, and Humans in China from 2004 to 2009Journal of Virology, 2010
- Adaptive strategies of the influenza virus polymerase for replication in humansProceedings of the National Academy of Sciences, 2009
- Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and MiceScience, 2009
- Pathogenesis and Transmission of Swine-Origin 2009 A(H1N1) Influenza Virus in FerretsScience, 2009
- In vitro and in vivo characterization of new swine-origin H1N1 influenza virusesNature, 2009
- Human HA and polymerase subunit PB2 proteins confer transmission of an avian influenza virus through the airProceedings of the National Academy of Sciences, 2009
- High Temperature (30°C) Blocks Aerosol but Not Contact Transmission of Influenza VirusJournal of Virology, 2008
- Properties and Dissemination of H5N1 Viruses Isolated during an Influenza Outbreak in Migratory Waterfowl in Western ChinaJournal of Virology, 2006
- A DNA transfection system for generation of influenza A virus from eight plasmidsProceedings of the National Academy of Sciences, 2000