Growth of H5N1 influenza A viruses in the upper respiratory tracts of mice

• Published in: PLoS pathogens 2007-10, Vol.3 (10), p.1374-1379
• Main Authors: Hatta, Masato, Hatta, Yasuko, Kim, Jin Hyun, Watanabe, Shinji, Shinya, Kyoko, Nguyen, Tung, Lien, Phuong Song, Le, Quynh Mai, Kawaoka, Yoshihiro
• Format: Article
• Language: English
• Subjects: Animals; Avian influenza viruses; Birds; Causes of; Cell Line; Genes; Growth; Health aspects; Humans; In Vitro; Influenza A Virus, H5N1 Subtype - pathogenicity; Influenza A Virus, H5N1 Subtype - physiology; Mice; Mice, Inbred BALB C; Mus (mouse); Mutation; Orthomyxoviridae Infections - genetics; Orthomyxoviridae Infections - virology; Pandemics; Polymerase Chain Reaction; Proteins; Respiratory tract infections; Respiratory Tract Infections - genetics; Respiratory Tract Infections - virology; RNA Replicase - genetics; Viral Proteins - chemistry; Viral Proteins - genetics; Virology; Virus Replication; Viruses
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.0030133

Highly pathogenic avian H5N1 influenza A viruses have spread throughout Asia, Europe, and Africa, raising serious worldwide concern about their pandemic potential. Although more than 250 people have been infected with these viruses, with a consequent high rate of mortality, the molecular mechanisms responsible for the efficient transmission of H5N1 viruses among humans remain elusive. We used a mouse model to examine the role of the amino acid at position 627 of the PB2 viral protein in efficient replication of H5N1 viruses in the mammalian respiratory tract. Viruses possessing Lys at position 627 of PB2 replicated efficiently in lungs and nasal turbinates, as well as in cells, even at the lower temperature of 33 degrees C. Those viruses possessing Glu at this position replicated less well in nasal turbinates than in lungs, and less well in cells at the lower temperature. These results suggest that Lys at PB2-627 confers to avian H5N1 viruses the advantage of efficient growth in the upper and lower respiratory tracts of mammals. Therefore, efficient viral growth in the upper respiratory tract may provide a platform for the adaptation of avian H5N1 influenza viruses to humans and for efficient person-to-person virus transmission, in the context of changes in other viral properties including specificity for human (sialic acid alpha-2,6-galactose containing) receptors.