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.

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Authors

Zhang Y, Zhang Q, Gao Y, He X, Kong H, Jiang Y, Guan Y, Xia X, Shu Y, Kawaoka Y, Bu Z, Chen H

Institution

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.

Source

Journal of virology 86:18 2012 Sep pg 9666-74

MeSH

Amino Acid Substitution
Animals
Cricetinae
Disease Models, Animal
Female
Ferrets
Genes, Viral
Hemagglutinin Glycoproteins, Influenza Virus
Host-Pathogen Interactions
Humans
Influenza A Virus, H1N1 Subtype
Influenza, Human
Lung
Orthomyxoviridae Infections
Pandemics
Polysaccharides
RNA Replicase
Receptors, Virus
Swine
Viral Proteins
Virulence
Virus Replication

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22740390