Transmission of Influenza Virus in a Mammalian Host Is Increased by PB2 Amino Acids 627K or 627E/701N

By J. Steel, Anice C. Lowen, S. Mubareka, P. Palese. PLoS Pathogens, 2009

610 citations recorded by the source corpus.

Since 2003, more than 380 cases of H5N1 influenza virus infection of humans have been reported. Although the resultant disease in these cases was often severe or fatal, transmission of avian influenza viruses between humans is rare. The precise nature of the barrier blocking human-to-human spread is unknown. It is clear, however, that efficient human-to-human transmission of an antigenically novel influenza virus would result in a pandemic. Influenza viruses with changes at amino acids 627 or 701 of the PB2 protein have been isolated from human cases of highly pathogenic H5 and H7 avian influenza. Herein, we have used the guinea pig model to test the contributions of PB2 627 and 701 to mammalian transmission. To this end, viruses carrying mutations at these positions were generated in the A/Panama/2007/99 (H3N2) and A/Viet Nam/1203/04 (H5N1) backgrounds. In the context of either rPan99 or rVN1203, mutation of lysine 627 to the avian consensus residue glutamic acid was found to decrease transmission. Introduction of an asparagine at position 701, in conjunction with the K627E mutation, resulted in a phenotype more similar to that of the parental strains, suggesting that this residue can compensate for the lack of 627K in terms of increasing transmission in mammals. Thus, our data show that PB2 amino acids 627 and 701 are determinants of mammalian inter-host transmission in diverse virus backgrounds.

Subfields: Agronomy and Crop Science, Epidemiology

View Paper: https://www.semanticscholar.org/paper/92ed75017d2d6eb44edc369fb6e281b4c7ed051c

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In Agronomy and Crop Science

1. J. Taubenberger
2. Raymond Tellier
3. J. Kash

In Epidemiology

1. A. García‐Sastre
2. J. Taubenberger
3. J. Kash
4. R. Medina
5. Raymond Tellier

Citations in the corpus

• Influenza A viruses: new research developments (2011, background): “Efficient human–human transmission of HPAI H5N1 viruses has not occurred efficiently in nature or in experimental mammalian models of transmissio”
• Influenza Virus Evolution, Host Adaptation and Pandemic Formation (2010, background): “…PB2 implicated in nuclear localization (Gabriel et al., 2008; Tarendeau et al., 2007), have similarly been identified as a host-adaptive locus (Gabriel et al., 2005), with the D701N mutation increasing both replication in mice (Li et al., 2005) and transmission in guinea pigs (Steel et al., 2009).”
• Aerosol transmission of influenza A virus: a review of new studies (2009, methodology): “Using the guinea pig model, Steel and colleagues also showed how mutations in the PB2 gene allow for efficient transmission, including through the large droplet and/or aerosol route (Steel et al. 2009).”