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Minimal molecular constraints for respiratory droplet transmission of an avian-human H9N2 influenza A virus.
Proc Natl Acad Sci U S A 2009; 106(18):7565-70PN

Abstract

Pandemic influenza requires interspecies transmission of an influenza virus with a novel hemagglutinin (HA) subtytpe that can adapt to its new host through either reassortment or point mutations and transmit by aerosolized respiratory droplets. Two previous pandemics of 1957 and 1968 resulted from the reassortment of low pathogenic avian viruses and human subtypes of that period; however, conditions leading to a pandemic virus are still poorly understood. Given the endemic situation of avian H9N2 influenza with human-like receptor specificity in Eurasia and its occasional transmission to humans and pigs, we wanted to determine whether an avian-human H9N2 reassortant could gain respiratory transmission in a mammalian animal model, the ferret. Here we show that following adaptation in the ferret, a reassortant virus carrying the surface proteins of an avian H9N2 in a human H3N2 backbone can transmit efficiently via respiratory droplets, creating a clinical infection similar to human influenza infections. Minimal changes at the protein level were found in this virus capable of respiratory droplet transmission. A reassortant virus expressing only the HA and neuraminidase (NA) of the ferret-adapted virus was able to account for the transmissibility, suggesting that currently circulating avian H9N2 viruses require little adaptation in mammals following acquisition of all human virus internal genes through reassortment. Hemagglutinin inhibition (HI) analysis showed changes in the antigenic profile of the virus, which carries profound implications for vaccine seed stock preparation against avian H9N2 influenza. This report illustrates that aerosolized respiratory transmission is not exclusive to current human H1, H2, and H3 influenza subtypes.

Authors+Show Affiliations

Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, 8075 Greenmead Drive, College Park, MD 20742, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19380727

Citation

Sorrell, Erin M., et al. "Minimal Molecular Constraints for Respiratory Droplet Transmission of an Avian-human H9N2 Influenza a Virus." Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 18, 2009, pp. 7565-70.
Sorrell EM, Wan H, Araya Y, et al. Minimal molecular constraints for respiratory droplet transmission of an avian-human H9N2 influenza A virus. Proc Natl Acad Sci USA. 2009;106(18):7565-70.
Sorrell, E. M., Wan, H., Araya, Y., Song, H., & Perez, D. R. (2009). Minimal molecular constraints for respiratory droplet transmission of an avian-human H9N2 influenza A virus. Proceedings of the National Academy of Sciences of the United States of America, 106(18), pp. 7565-70. doi:10.1073/pnas.0900877106.
Sorrell EM, et al. Minimal Molecular Constraints for Respiratory Droplet Transmission of an Avian-human H9N2 Influenza a Virus. Proc Natl Acad Sci USA. 2009 May 5;106(18):7565-70. PubMed PMID: 19380727.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Minimal molecular constraints for respiratory droplet transmission of an avian-human H9N2 influenza A virus. AU - Sorrell,Erin M, AU - Wan,Hongquan, AU - Araya,Yonas, AU - Song,Haichen, AU - Perez,Daniel R, Y1 - 2009/04/20/ PY - 2009/4/22/entrez PY - 2009/4/22/pubmed PY - 2009/5/30/medline SP - 7565 EP - 70 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 106 IS - 18 N2 - Pandemic influenza requires interspecies transmission of an influenza virus with a novel hemagglutinin (HA) subtytpe that can adapt to its new host through either reassortment or point mutations and transmit by aerosolized respiratory droplets. Two previous pandemics of 1957 and 1968 resulted from the reassortment of low pathogenic avian viruses and human subtypes of that period; however, conditions leading to a pandemic virus are still poorly understood. Given the endemic situation of avian H9N2 influenza with human-like receptor specificity in Eurasia and its occasional transmission to humans and pigs, we wanted to determine whether an avian-human H9N2 reassortant could gain respiratory transmission in a mammalian animal model, the ferret. Here we show that following adaptation in the ferret, a reassortant virus carrying the surface proteins of an avian H9N2 in a human H3N2 backbone can transmit efficiently via respiratory droplets, creating a clinical infection similar to human influenza infections. Minimal changes at the protein level were found in this virus capable of respiratory droplet transmission. A reassortant virus expressing only the HA and neuraminidase (NA) of the ferret-adapted virus was able to account for the transmissibility, suggesting that currently circulating avian H9N2 viruses require little adaptation in mammals following acquisition of all human virus internal genes through reassortment. Hemagglutinin inhibition (HI) analysis showed changes in the antigenic profile of the virus, which carries profound implications for vaccine seed stock preparation against avian H9N2 influenza. This report illustrates that aerosolized respiratory transmission is not exclusive to current human H1, H2, and H3 influenza subtypes. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/19380727/Minimal_molecular_constraints_for_respiratory_droplet_transmission_of_an_avian_human_H9N2_influenza_A_virus_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=19380727 DB - PRIME DP - Unbound Medicine ER -