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


CONCLUSIONS
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.
Sun
Lijing
L
Division of Molecular Biotechnology, Helmholtz-Centre for Infection Research, Inhoffenstr 7, 38124 Braunschweig, Germany.
Hemgård
Gun-Viol
GV
Susanto
Sony A
SA
Wirth
Manfred
M
D000595:Amino Acid Sequence; D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D011485:Protein Binding; D016415:Sequence Alignment; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication; D000086082:Viroporin Proteins
D051242:Caveolin 1; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins