tailieunhanh - Báo cáo y học: "Caveolin-1 influences human influenza A virus (H1N1) multiplication in cell culture"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Caveolin-1 influences human influenza A virus (H1N1) multiplication in cell culture | Sun et al. Virology Journal 2010 7 108 http content 7 1 108 VIROLOGY JOURNAL RESEARCH Open Access Caveolin-1 influences human influenza A virus H1N1 multiplication in cell culture Lijing Sun 1 2 3 Gun-Viol Hemgârd1 Sony A Susanto1 and Manfred Wirth 1 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. Pulldown 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. Background In the last few years the .