Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8751718 | Virus Research | 2018 | 9 Pages |
Abstract
The protein VCP/p97 (also named CDC48 and TER94) belongs to a type II subfamily of the AAA+ATPases and controls cellular proteostasis by acting upstream of proteasomes in the ubiquitin-proteasome protein degradation pathway. The function of VCP/p97 in the baculovirus infection cycle in insect cells remains unknown. Here, we identified VCP/p97 in the fall armyworm Spodoptera frugiperda (Sf9) cells and analyzed the replication of the Autographa californica multiple nucleopolyhedrovirus, AcMNPV, in Sf9 cells in which the VCP/p97 function was inhibited. The specific allosteric inhibitor of the VCP/p97 ATPase activity, NMS-873, did not deplete VCP/p97 in infected cells but caused a dose-dependent inhibition of viral DNA synthesis and efficiently suppressed expression of viral proteins and production of budded virions. NMS-873 caused accumulation of ubiquitinated proteins in a manner similar to the inhibitor of proteasome activity, Bortezomib. This suggests the essential function of VCP/p97 in the baculovirus infection cycle might be associated, at least in part, with the ubiquitin-proteasome system.
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Authors
Yulia V. Lyupina, Pavel A. Erokhov, Oksana I. Kravchuk, Alexander D. Finoshin, Svetlana B. Abaturova, Olga V. Orlova, Svetlana N. Beljelarskaya, Margarita V. Kostyuchenko, Victor S. Mikhailov,