HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data Buy All Versions of this Article: fj.09-134072v1 23/10/3377    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Liu, N. Articles by Cai, Z. PubMed PubMed Citation Articles by Liu, N. Articles by Cai, Z.

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

Ning Liu^*,, Genyan Wang, Kim Chung Lee^*, Yi Guan^,, Honglin Chen^,,1 and Zongwei Cai^*,1

^* Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China;

Jilin University, Changchun, China;

International Institute of Infection and Immunity, Shantou University, Shantou, China;

State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology and the Research Center of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, China

¹ Correspondence: Z.C., Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China. E-mail: zwcai{at}hkbu.edu.hk; H.C., State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, University of Hong Kong, Hong Kong SAR, China. E-mail: hlchen{at}hkucc.hku.hk

Influenza A viruses are RNA viruses that contain negative-sense, single-stranded, and segmented RNA genome, which depends on virally encoded RNA-dependent 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.—Liu, N., Wang, G., Lee, K. C., Guan, Y., Chen, H., Cai, Z. Mutations in influenza virus replication and transcription: detection of amino acid substitutions in hemagglutinin of an avian influenza virus (H1N1).

Key Words: polymorphism of viral antigen • mass spectrometric sequencing • infection • receptor • mutation • replication and transcription