Mutations in the NS1 C-terminal tail do not enhance replication or virulence of the 2009 pandemic H1N1 influenza A virus

Benjamin G Hale; John Steel; Balaji Manicassamy; Rafael A Medina; Jianqiang Ye; Danielle Hickman; Anice C Lowen; Daniel R Perez; Adolfo García-Sastre

doi:10.1099/vir.0.020925-0

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Mutations in the NS1 C-terminal tail do not enhance replication or virulence of the 2009 pandemic H1N1 influenza A virus

Journal article

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Mutations in the NS1 C-terminal tail do not enhance replication or virulence of the 2009 pandemic H1N1 influenza A virus

Benjamin G Hale, John Steel, Balaji Manicassamy, Rafael A Medina, Jianqiang Ye, Danielle Hickman, Anice C Lowen, Daniel R Perez and Adolfo García-Sastre

Journal of general virology, Vol.91(Pt 7), pp.1737-1742

07/2010

DOI: 10.1099/vir.0.020925-0

PMCID: PMC3052525

PMID: 20237225

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Abstract

The ‘classical’ swine H1N1 influenza A virus lineage was established after the devastating 1918 human pandemic virus entered domestic pig herds. A descendent of this lineage recently re-emerged in humans as the 2009 pandemic H1N1 virus. Adaptation in pigs has led to several changes in the multifunctional viral NS1 protein as compared with the parental 1918 virus, most notably a K217E substitution that abolishes binding to host Crk/CrkL signalling adapters, and an 11 aa C-terminal truncation. Using reverse genetics, we reintroduced both these features into a prototype 2009 H1N1 strain, A/California/04/09. Restoration of Crk/CrkL binding or extension of NS1 to 230 aa had no impact on virus replication in human or swine cells. In addition, minimal effects on replication, pathogenicity and transmission were observed in mouse and ferret models. Our data suggest that the currently circulating 2009 H1N1 virus is optimized to replicate efficiently without requiring certain NS1 functions.

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Title: Subtitle: Mutations in the NS1 C-terminal tail do not enhance replication or virulence of the 2009 pandemic H1N1 influenza A virus
Creators: Benjamin G Hale - Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
John Steel - Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
Balaji Manicassamy - Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
Rafael A Medina - Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
Jianqiang Ye - Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA
Danielle Hickman - Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA
Anice C Lowen - Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
Daniel R Perez - Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA
Adolfo García-Sastre - Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
Resource Type: Journal article
Publication Details: Journal of general virology, Vol.91(Pt 7), pp.1737-1742
DOI: 10.1099/vir.0.020925-0
PMID: 20237225
PMCID: PMC3052525
NLM abbreviation: J Gen Virol
ISSN: 0022-1317
eISSN: 1465-2099
Publisher: Society for General Microbiology
Language: English
Date published: 07/2010
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083269702771

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