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Increased pathogenicity of a reassortant 2009 pandemic H1N1 influenza virus containing an H5N1 hemagglutinin.
J Virol. 2011 Dec; 85(23):12262-70.JV

Abstract

A novel H1N1 influenza virus emerged in 2009 (pH1N1) to become the first influenza pandemic of the 21st century. This virus is now cocirculating with highly pathogenic H5N1 avian influenza viruses in many parts of the world, raising concerns that a reassortment event may lead to highly pathogenic influenza strains with the capacity to infect humans more readily and cause severe disease. To investigate the virulence of pH1N1-H5N1 reassortant viruses, we created pH1N1 (A/California/04/2009) viruses expressing individual genes from an avian H5N1 influenza strain (A/Hong Kong/483/1997). Using several in vitro models of virus replication, we observed increased replication for a reassortant CA/09 virus expressing the hemagglutinin (HA) gene of HK/483 (CA/09-483HA) relative to that of either parental CA/09 virus or reassortant CA/09 expressing other HK/483 genes. This increased replication correlated with enhanced pathogenicity in infected mice similar to that of the parental HK/483 strain. The serial passage of the CA/09 parental virus and the CA/09-483HA virus through primary human lung epithelial cells resulted in increased pathogenicity, suggesting that these viruses easily adapt to humans and become more virulent. In contrast, serial passage attenuated the parental HK/483 virus in vitro and resulted in slightly reduced morbidity in vivo, suggesting that sustained replication in humans attenuates H5N1 avian influenza viruses. Taken together, these data suggest that reassortment between cocirculating human pH1N1 and avian H5N1 influenza strains will result in a virus with the potential for increased pathogenicity in mammals.

Authors+Show Affiliations

Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21917948

Citation

Cline, Troy D., et al. "Increased Pathogenicity of a Reassortant 2009 Pandemic H1N1 Influenza Virus Containing an H5N1 Hemagglutinin." Journal of Virology, vol. 85, no. 23, 2011, pp. 12262-70.
Cline TD, Karlsson EA, Freiden P, et al. Increased pathogenicity of a reassortant 2009 pandemic H1N1 influenza virus containing an H5N1 hemagglutinin. J Virol. 2011;85(23):12262-70.
Cline, T. D., Karlsson, E. A., Freiden, P., Seufzer, B. J., Rehg, J. E., Webby, R. J., & Schultz-Cherry, S. (2011). Increased pathogenicity of a reassortant 2009 pandemic H1N1 influenza virus containing an H5N1 hemagglutinin. Journal of Virology, 85(23), 12262-70. https://doi.org/10.1128/JVI.05582-11
Cline TD, et al. Increased Pathogenicity of a Reassortant 2009 Pandemic H1N1 Influenza Virus Containing an H5N1 Hemagglutinin. J Virol. 2011;85(23):12262-70. PubMed PMID: 21917948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased pathogenicity of a reassortant 2009 pandemic H1N1 influenza virus containing an H5N1 hemagglutinin. AU - Cline,Troy D, AU - Karlsson,Erik A, AU - Freiden,Pamela, AU - Seufzer,Bradley J, AU - Rehg,Jerold E, AU - Webby,Richard J, AU - Schultz-Cherry,Stacey, Y1 - 2011/09/14/ PY - 2011/9/16/entrez PY - 2011/9/16/pubmed PY - 2012/1/20/medline SP - 12262 EP - 70 JF - Journal of virology JO - J Virol VL - 85 IS - 23 N2 - A novel H1N1 influenza virus emerged in 2009 (pH1N1) to become the first influenza pandemic of the 21st century. This virus is now cocirculating with highly pathogenic H5N1 avian influenza viruses in many parts of the world, raising concerns that a reassortment event may lead to highly pathogenic influenza strains with the capacity to infect humans more readily and cause severe disease. To investigate the virulence of pH1N1-H5N1 reassortant viruses, we created pH1N1 (A/California/04/2009) viruses expressing individual genes from an avian H5N1 influenza strain (A/Hong Kong/483/1997). Using several in vitro models of virus replication, we observed increased replication for a reassortant CA/09 virus expressing the hemagglutinin (HA) gene of HK/483 (CA/09-483HA) relative to that of either parental CA/09 virus or reassortant CA/09 expressing other HK/483 genes. This increased replication correlated with enhanced pathogenicity in infected mice similar to that of the parental HK/483 strain. The serial passage of the CA/09 parental virus and the CA/09-483HA virus through primary human lung epithelial cells resulted in increased pathogenicity, suggesting that these viruses easily adapt to humans and become more virulent. In contrast, serial passage attenuated the parental HK/483 virus in vitro and resulted in slightly reduced morbidity in vivo, suggesting that sustained replication in humans attenuates H5N1 avian influenza viruses. Taken together, these data suggest that reassortment between cocirculating human pH1N1 and avian H5N1 influenza strains will result in a virus with the potential for increased pathogenicity in mammals. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/21917948/Increased_pathogenicity_of_a_reassortant_2009_pandemic_H1N1_influenza_virus_containing_an_H5N1_hemagglutinin_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=21917948 DB - PRIME DP - Unbound Medicine ER -