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Essential Function of VCP/p97 in Infection Cycle of the Nucleopolyhedrovirus AcMNPV in Spodoptera Frugiperda Sf9 Cells

Essential Function of VCP/p97 in Infection Cycle of the Nucleopolyhedrovirus AcMNPV in Spodoptera Frugiperda Sf9 Cells

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

Virus Res. 2018 Jul 15;253:68-76.

PMID: 29890203

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1418013758	NMS-873		1418013-75-8	Price

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