Variations in the Hemagglutinin of the 2009 H1N1 Pandemic Virus: Potential for Strains with Altered Virulence Phenotype?

Details

• Alternative Title:
  PLoS Pathog
• Personal Author:
  Ye, Jianqiang ; Sorrell, Erin M. ; Cai, Yibin ; Shao, Hongxia ; Xu, Kemin ; Pena, Lindomar ; Hickman, Danielle ; Song, Haichen ; Angel, Matthew ; Medina, Rafael A. ; Manicassamy, Balaji ; Garcia-Sastre, Adolfo ; Perez, Daniel R.
• Description:
  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.
• Subjects:
  Animals Cells, Cultured Dogs Female Ferrets Genetic Association Studies Genetic Variation Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza, Human Influenza A Virus, H1N1 Subtype Mice Mice, Inbred BALB C Mice, Inbred DBA Models, Molecular Pandemics Phenotype Protein Conformation Virulence

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• Source:
  PLoS Pathog. 6(10).
• Pubmed ID:
  20976194
• Pubmed Central ID:
  PMC2954835
• Document Type:
  Journal Article
• Funding:
  1U01CI000355/CI/NCPDCID CDC HHS/United States ; HHSN266186700010C/PHS HHS/United States ; R01AI052155/AI/NIAID NIH HHS/United States
• Volume:
  6
• Issue:
  10
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:d49d9a2bfdb083779134781268133b6f0c2db8274d368c1d49aac3418579d20f
• Download URL:
  https://stacks.cdc.gov/view/cdc/22875/cdc_22875_DS1.pdf
• File Type:
  [PDF - 3.88 MB ]