Home LiteratureArticle Details
PMID: 21325408 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Impact of amino acid mutations in PB2, PB1-F2, and NS1 on the replication and pathogenicity of pandemic (H1N1) 2009 influenza viruses.

Journal of virology ·Vol. 85 ·No. 9 ·2011-05-00 ·Pages 4596-601

Ozawa M, Basnet S, Burley LM, Neumann G, Hatta M, Kawaoka Y

Abstract

Here, we assessed the effects of PB1-F2 and NS1 mutations known to increase the pathogenicity of influenza viruses on the replication and pathogenicity in mice of pandemic (H1N1) 2009 influenza viruses. We also characterized viruses possessing a PB1-F2 mutation that was recently identified in pandemic (H1N1) 2009 influenza virus isolates, with and without simultaneous mutations in PB2 and NS1. Our results suggest that some NS1 mutations and the newly identified PB1-F2 mutation have the potential to increase the replication and/or pathogenicity of pandemic (H1N1) 2009 influenza viruses.

MeSH Terms
Amino Acid Substitution/genetics Animals Influenza A Virus, H1N1 Subtype/genetics,isolation & purification,pathogenicity Mice Orthomyxoviridae Infections/pathology,virology Viral Nonstructural Proteins/genetics,metabolism Viral Proteins/genetics,metabolism Virulence Virus Replication
Chemicals
INS1 protein, influenza virus PB1-F2 protein, Influenza A virus PB2 protein, influenza virus Viral Nonstructural Proteins Viral Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ozawa Makoto
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 575 Science Drive, Madison, WI 53711, USA.
Basnet Sarmila
Burley Lisa M
Neumann Gabriele
Hatta Masato
Kawaoka Yoshihiro
References (28)
28 references, click to expand
  1. A new influenza virus virulence determinant: the NS1 protein four C-terminal residues modulate pathogenicity.
    Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4381-6 PMID: 18334632
  2. A novel influenza A virus mitochondrial protein that induces cell death.
    Nat Med. 2001 Dec;7(12):1306-12 PMID: 11726970
  3. Influenza A virus PB1-F2 protein contributes to viral pathogenesis in mice.
    J Virol. 2006 Aug;80(16):7976-83 PMID: 16873254
  4. Generation of influenza A viruses entirely from cloned cDNAs.
    Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9345-50 PMID: 10430945
  5. Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems.
    Virology. 1998 Dec 20;252(2):324-30 PMID: 9878611
  6. Selection of H5N1 influenza virus PB2 during replication in humans.
    J Virol. 2009 May;83(10):5278-81 PMID: 19264775
  7. Use of single-gene reassortant viruses to study the role of avian influenza A virus genes in attenuation of wild-type human influenza A virus for squirrel monkeys and adult human volunteers.
    J Clin Microbiol. 1992 Mar;30(3):655-62 PMID: 1551982
  8. A novel influenza A (H1N1) vaccine in various age groups.
    N Engl J Med. 2009 Dec 17;361(25):2414-23 PMID: 19846844
  9. A single amino acid in the PB2 gene of influenza A virus is a determinant of host range.
    J Virol. 1993 Apr;67(4):1761-4 PMID: 8445709
  10. PB1-F2 expression by the 2009 pandemic H1N1 influenza virus has minimal impact on virulence in animal models.
    J Virol. 2010 May;84(9):4442-50 PMID: 20181699
  11. PDZ domains and the organization of supramolecular complexes.
    Annu Rev Neurosci. 2001;24:1-29 PMID: 11283303
  12. PB2 amino acid at position 627 affects replicative efficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in mice.
    Virology. 2004 Mar 15;320(2):258-66 PMID: 15016548
  13. Emergence of a novel swine-origin influenza A (H1N1) virus in humans.
    N Engl J Med. 2009 Jun 18;360(25):2605-15 PMID: 19423869
  14. Biological and structural characterization of a host-adapting amino acid in influenza virus.
    PLoS Pathog. 2010 Aug 05;6(8):e1001034 PMID: 20700447
  15. In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses.
    Nature. 2009 Aug 20;460(7258):1021-5 PMID: 19672242
  16. The multifunctional NS1 protein of influenza A viruses.
    J Gen Virol. 2008 Oct;89(Pt 10):2359-2376 PMID: 18796704
  17. A single mutation in the PB1-F2 of H5N1 (HK/97) and 1918 influenza A viruses contributes to increased virulence.
    PLoS Pathog. 2007 Oct 5;3(10):1414-21 PMID: 17922571
  18. Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model.
    J Virol. 2005 Sep;79(18):12058-64 PMID: 16140781
  19. Immunogenicity of a monovalent 2009 influenza A(H1N1) vaccine in infants and children: a randomized trial.
    JAMA. 2010 Jan 6;303(1):37-46 PMID: 20026597
  20. Differential polymerase activity in avian and mammalian cells determines host range of influenza virus.
    J Virol. 2007 Sep;81(17):9601-4 PMID: 17567688
  21. Virulence determinants of avian H5N1 influenza A virus in mammalian and avian hosts: role of the C-terminal ESEV motif in the viral NS1 protein.
    J Virol. 2010 Oct;84(20):10708-18 PMID: 20686040
  22. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009.
    N Engl J Med. 2009 Nov 12;361(20):1935-44 PMID: 19815859
  23. PB1-F2 proteins from H5N1 and 20 century pandemic influenza viruses cause immunopathology.
    PLoS Pathog. 2010 Jul 22;6(7):e1001014 PMID: 20661425
  24. Large-scale sequence analysis of avian influenza isolates.
    Science. 2006 Mar 17;311(5767):1576-80 PMID: 16439620
  25. Response to a monovalent 2009 influenza A (H1N1) vaccine.
    N Engl J Med. 2009 Dec 17;361(25):2405-13 PMID: 19745216
  26. Transmission and pathogenesis of swine-origin 2009 A(H1N1) influenza viruses in ferrets and mice.
    Science. 2009 Jul 24;325(5939):484-7 PMID: 19574347
  27. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses.
    Science. 2001 Sep 7;293(5536):1840-2 PMID: 11546875
  28. Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets.
    Science. 2009 Jul 24;325(5939):481-3 PMID: 19574348
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
1098-5514
DOI
10.1128/JVI.00029-11
Published
2011-05-00
Epub
2011-00-16
Pages
4596-601
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC3126221
Subset
IM
Grants
NIAID NIH HHS · HHSN266200700010C · United States
PHS HHS · 266200700010C · United States
External Links
PubMed source DOI: 10.1128/JVI.00029-11 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2