Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?

Jianqiang Ye; Erin M Sorrell; Yibin Cai; Hongxia Shao; Kemin Xu; Lindomar Pena; Danielle Hickman; Haichen Song; Matthew Angel; Rafael A Medina; Balaji Manicassamy; Adolfo Garcia-Sastre; Daniel R Perez

doi:10.1371/journal.ppat.1001145

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Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?

Journal article

Open access

Peer reviewed

Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?

Jianqiang Ye, Erin M Sorrell, Yibin Cai, Hongxia Shao, Kemin Xu, Lindomar Pena, Danielle Hickman, Haichen Song, Matthew Angel, Rafael A Medina, …

PLoS pathogens, Vol.6(10), pp.e1001145-e1001145

10/14/2010

DOI: 10.1371/journal.ppat.1001145

PMCID: PMC2954835

PMID: 20976194

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Abstract

A novel, swine-origin influenza H1N1 virus (H1N1pdm) caused the first pandemic of the 21st century. This pandemic, although efficient in transmission, is mild in virulence. This atypical mild pandemic season has raised concerns regarding the potential of this virus to acquire additional virulence markers either through further adaptation or possibly by immune pressure in the human host. Using the mouse model we generated, within a single round of infection with A/California/04/09/H1N1 (Ca/04), a virus lethal in mice--herein referred to as mouse-adapted Ca/04 (ma-Ca/04). Five amino acid substitutions were found in the genome of ma-Ca/04: 3 in HA (D131E, S186P and A198E), 1 in PA (E298K) and 1 in NP (D101G). Reverse genetics analyses of these mutations indicate that all five mutations from ma-Ca/04 contributed to the lethal phenotype; however, the D131E and S186P mutations--which are also found in the 1918 and seasonal H1N1 viruses-in HA alone were sufficient to confer virulence of Ca/04 in mice. HI assays against H1N1pdm demonstrate that the D131E and S186P mutations caused minor antigenic changes and, likely, affected receptor binding. The rapid selection of ma-Ca/04 in mice suggests that a virus containing this constellation of amino acids might have already been present in Ca/04, likely as minor quasispecies.

Influenza A Virus, H1N1 Subtype - immunology

Pandemics

Humans

Hemagglutinin Glycoproteins, Influenza Virus - immunology

Genetic Variation - physiology

Hemagglutinin Glycoproteins, Influenza Virus - genetics

Virulence - genetics

Female

Influenza, Human - virology

Mice, Inbred DBA

Influenza A Virus, H1N1 Subtype - genetics

Hemagglutinin Glycoproteins, Influenza Virus - chemistry

Genetic Association Studies

Cells, Cultured

Models, Molecular

Influenza A Virus, H1N1 Subtype - pathogenicity

Influenza, Human - epidemiology

Ferrets

Phenotype

Animals

Influenza, Human - genetics

Dogs

Protein Conformation

Mice

Mice, Inbred BALB C

Influenza, Human - immunology

Details

Title: Subtitle: Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?
Creators: Jianqiang Ye - Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, United States of America
Erin M Sorrell
Yibin Cai
Hongxia Shao
Kemin Xu
Lindomar Pena
Danielle Hickman
Haichen Song
Matthew Angel
Rafael A Medina
Balaji Manicassamy
Adolfo Garcia-Sastre
Daniel R Perez
Resource Type: Journal article
Publication Details: PLoS pathogens, Vol.6(10), pp.e1001145-e1001145
DOI: 10.1371/journal.ppat.1001145
PMID: 20976194
PMCID: PMC2954835
NLM abbreviation: PLoS Pathog
ISSN: 1553-7366
eISSN: 1553-7374
Publisher: Public Library of Science
Grant note: HHSN266186700010C / PHS HHS U01 CI000355 / NCPDCID CDC HHS 1U01CI000355 / NCPDCID CDC HHS R01 AI052155 / NIAID NIH HHS R01AI052155 / NIAID NIH HHS
Language: English
Date published: 10/14/2010
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083882802771

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