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Caveolin-1 influences human influenza A virus (H1N1) multiplication in cell culture

Lijing Sun123, Gun-Viol Hemgård1, Sony A Susanto1 and Manfred Wirth1*

Author Affiliations

1 Division of Molecular Biotechnology, Helmholtz-Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany

2 National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, No.1 Bei-er-tiao, 100080 Beijing, China

3 Graduate University of Chinese Academy of Sciences, 19A Yu Quan Rd, 100049 Beijing, China

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Virology Journal 2010, 7:108  doi:10.1186/1743-422X-7-108

Published: 26 May 2010

Abstract

Background

The threat of recurring influenza pandemics caused by new viral strains and the occurrence of escape mutants necessitate the search for potent therapeutic targets. The dependence of viruses on cellular factors provides a weak-spot in the viral multiplication strategy and a means to interfere with viral multiplication.

Results

Using a motif-based search strategy for antiviral targets we identified caveolin-1 (Cav-1) as a putative cellular interaction partner of human influenza A viruses, including the pandemic influenza A virus (H1N1) strains of swine origin circulating from spring 2009 on. The influence of Cav-1 on human influenza A/PR/8/34 (H1N1) virus replication was determined in inhibition and competition experiments. RNAi-mediated Cav-1 knock-down as well as transfection of a dominant-negative Cav-1 mutant results in a decrease in virus titre in infected Madin-Darby canine kidney cells (MDCK), a cell line commonly used in basic influenza research as well as in virus vaccine production. To understand the molecular basis of the phenomenon we focussed on the putative caveolin-1 binding domain (CBD) located in the lumenal, juxtamembranal portion of the M2 matrix protein which has been identified in the motif-based search. Pull-down assays and co-immunoprecipitation experiments showed that caveolin-1 binds to M2. The data suggest, that Cav-1 modulates influenza virus A replication presumably based on M2/Cav-1 interaction.

Conclusion

As Cav-1 is involved in the human influenza A virus life cycle, the multifunctional protein and its interaction with M2 protein of human influenza A viruses represent a promising starting point for the search for antiviral agents.