Inhibition of the ubiquitin-proteasome system affects influenza A virus infection at a postfusion step.

Widjaja, Ivy; de Vries, Erik; Tscherne, Donna M; García-Sastre, Adolfo; Rottier, Peter J M; de Haan, Cornelis A M

We have demonstrated that influenza A virus (IAV) RNA synthesis depends on the ubiquitin-proteasome system. IAV replication was reduced both by proteasome inhibitors and in E36ts20 cells, which contain the thermolabile ubiquitin-activating enzyme E1. While virus entry was not affected in E36ts20 cells, the proteasome inhibitor MG132 retained viral particles in the cytoplasm. Addition-removal experiments of MG132 in combination with bafilomycin A1, a well-established inhibitor of IAV entry and fusion, showed that MG132 affected IAV infection at a postfusion step. This was confirmed by the lack of inhibition of IAV entry by proteasome inhibitors in a virus-like particle fusion assay.