http://dx.doi.org/10.1096/fj.09-134072">
 

Document Type

Journal Article

Department/Unit

Department of Chemistry

Title

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

Language

English

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. © FASEB.

Keywords

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

Publication Date

2009

Source Publication Title

FASEB Journal

Volume

23

Issue

10

Start Page

3377

End Page

3382

Publisher

Federation of American Society of Experimental Biology

ISSN (print)

08926638

ISSN (electronic)

15306860

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