Inhibition of the ubiquitin-proteasome system affects influenza A virus infection at a postfusion step.
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.
Widjaja
Ivy
I
Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
de Vries
Erik
E
Tscherne
Donna M
DM
García-Sastre
Adolfo
A
Rottier
Peter J M
PJ
de Haan
Cornelis A M
CA
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D007976:Leupeptins / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology; D061988:Proteasome Inhibitors; D025801:Ubiquitin / Q000037:antagonists & inhibitors*; D014779:Virus Replication
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D007976:Leupeptins; D018942:Macrolides; D061988:Proteasome Inhibitors; D025801:Ubiquitin; C040929:bafilomycin A1; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde