Human HA and polymerase subunit PB2 proteins confer transmission of an avian influenza virus through the air

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 9; pp. 3366 - 3371
• Main Authors: Van Hoeven, Neal, Pappas, Claudia, Belser, Jessica A, Maines, Taronna R, Zeng, Hui, García-Sastre, Adolfo, Sasisekharan, Ram, Katz, Jacqueline M, Tumpey, Terrence M
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 03.03.2009; National Acad Sciences
• Subjects: Air Microbiology; airborne transmission; Animals; Avian flu; Avian influenza virus; Biological Sciences; Birds - virology; Cell Line; Disease transmission; Dogs; Enzymes; Ferrets; Ferrets - virology; Gene expression; Glycoproteins - metabolism; H1N1 subtype influenza A virus; H5N1 subtype influenza A virus; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; hemagglutinins; Humans; Influenza A virus; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - metabolism; Influenza in Birds - transmission; Influenza in Birds - virology; Influenza virus; Influenza, Human - transmission; Influenza, Human - virology; Male; Mustela; Mutation - genetics; Orthomyxoviridae; Pandemics; PB2 protein; Protein Subunits - metabolism; Proteins; Receptors; RNA Replicase - genetics; RNA Replicase - metabolism; RNA-directed RNA polymerase; Transmission efficiency; viral diseases of animals and humans; viral proteins; Viral Proteins - genetics; Viral Proteins - metabolism; virus replication; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0813172106

The influenza virus genes that confer efficient transmission of epidemic and pandemic strains in humans have not been identified. The rapid spread and severe disease caused by the 1918 influenza pandemic virus makes it an ideal virus to study the transmissibility of potentially pandemic influenza strains. Here, we used a series of human 1918-avian H1N1 influenza reassortant viruses to identify the genetic determinants that govern airborne transmission of avian influenza viruses. We have demonstrated that the 1918 HA gene was necessary for efficient direct contact transmission, but did not allow respiratory droplet transmission between ferrets of an avian influenza virus possessing an avian polymerase subunit PB2. The 1918 PB2 protein was found to be both necessary and sufficient for airborne transmission of a virus expressing the 1918 HA and neuraminidase. Also, it was found that influenza viruses that were able to transmit efficiently in ferrets were able to replicate efficiently at the lower temperature (33 °C) found in the environment of mammalian airway. These findings demonstrate that the adaptation of the HA and PB2 proteins are critical for the development of pandemic influenza strains from avian influenza viruses.