Mutations in influenza virus replication and transcription: Detection of amino acid substitutions in hemagglutinin of an avian influenza virus (H1N1)

Ning Liu, Genyan Wang, Chung Lee Kim, Yi Guan, Honglin Chen*, Zongwei CAI

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Influenza A viruses are RNA viruses that contain negative-sense, single-stranded, and segmented RNA genome, which depends on virally encoded RNAdependent RNA polymerase and cellular DNA-dependent RNA polymerase for replication of viral genome and transcription of viral mRNA, respectively. Hemagglutinin (HA), one of the major surface proteins of the influenza virus, is responsible for virus attachment to the receptor of host cells to initiate an infection. Amino acid (AA) substitutions in HA may cause changes in virus antigenicity and even receptor specificity. To detect the AA substitutions within HA at protein level, nanoelectrospray-MS/MS was used to analyze tryptic digestion of HA antigen directly purified from virus particles of an avian influenza virus, A/WDK/JX/12416/2005 (H1N1), of which the HA gene was sequenced as a reference. The comparison of the sequences obtained from analysis of viral genome and peptide found seven variations between HA gene and protein, namely E103K, R130K, T169I, I338V, N387S, S398I/L, and I399S in HA. Because influenza virus uses different polymerase machineries for replication and transcription, these substitutions could be introduced in the viral genome through replication process but not in viral mRNA in the transcription. The results, for the first time, provided experimental evidence showing differences in AA sequence obtained from direct analysis of viral protein derived from viral genome.

Original languageEnglish
Pages (from-to)3377-3382
Number of pages6
JournalFASEB Journal
Volume23
Issue number10
DOIs
Publication statusPublished - Oct 2009

Scopus Subject Areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

User-Defined Keywords

  • Infection
  • Mass spectrometric sequencing
  • Mutation
  • Polymorphism of viral antigen
  • Receptor
  • Replication and transcription

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