Role of ubiquitin-proteasome pathway in budded virus egress and GP64 surface distribution in Bombyx mori nucleopolyhedrovirus.

The Bombyx mori nucleopolyhedrovirus (BmNPV) is a DNA virus that affects the silkworm, B. mori, causing substantial economic losses in sericulture. This study investigates the mechanisms underlying budded virus egress, focusing on the roles of the ubiquitin-proteasome pathway (UPP) machinery. BmNPV produces two virion types: budded virions (BVs) and occlusion-derived virions (ODVs), which differ in their envelope origins and functions. Recent findings suggest similarities in the budding pathways of BmNPV and Autographa californica multiple nucleopolyhedrovirus (AcMNPV), involving plasma membrane budding and multivesicular body (MVB) pathways. The study reveals that specific UPP-related proteins, including 26S proteasome non-ATPase regulatory subunit 14 (PSMD14), polyubiquitin, proteasome alpha subunit 6 (PSMA6) and proteasome zeta subunit (PSMZ), are involved in BV egress. Using recombinant viruses and UPP inhibitors, we demonstrate the necessity of these proteins for GP64 secretion and effective BV release. RNA interference and cell surface display of GP64 analyses further validate the critical role of UPP in BmNPV BV egress and protein secretion. This research enhances our understanding of the mechanisms behind BmNPV MVB budding and GP64 secretion while also identifying potential targets for controlling the virus in sericulture.