Ubiquitin-proteasome Pathway and Virus Infection
泛素-蛋白水解酶复合体通路与病毒侵染

Ubiquitin is highly conserved 76 amino acid protein found in all eukaryotic orga nisms and ubiquitin-proteasome pathway (UPP) plays a very important role in reg ulated non-lysosomal ATP dependent protein degradation. This pathway pa rticipates in or regulates numerous cellular processes, such as selective protei n degradation, cell cycle progression, apoptosis, signal transduction, transcrip tional regulation, receptor control by endocytosis, immune response and the proc essing of antigens. Nevertheless, roles of UPP in virus infection are only begin ning to be clarified. Ubiquitin homology has also been found in insect viruses. All viral ubiquitin genes encode an N-terminal ubiquitin sequence and 3-256 am ino acids C-terminal peptides. Most of the residues known to be essential for u biq uitin function have been conserved in the viral variant. In Autographa californi ca nucleopolyhedrovirus (AcMNPV), viral ubiquitin is attached to the inner surfa ce of budded viron membrane by a covalently linked phospholipid and is not essen tial for viral replication. Currently, insect viruses are the only viruses known to encode ubiquitin. However, ubiquitin also plays a role in the life cycle of other viruses. Host ubiquitin molecules have been found in some plant viruses an d other animal viruses. Additionally, Africa swine fever virus (ASFV) encodes a ubiquitin-conjugating enzyme (E2) and a putative causal link between human immu nodeficiency virus type 1 (HIV-1) and ubiquitin was established by showing that depletion of the intracellular pool of free ubiquitin inhibits the virus buddin g. Further analyses indicated that many retroviruses proteins which are required for efficient pinching off the virus bud contain a late domain. The core elemen t of the late domain is a proline-rich motif (PPXY) which mediates the late dom ain to be ubiquitinated by cellular proteins. Recently, it has been shown that m any retroviruses have developed mechanisms to escape the cellular immune respons e, to facilitate virus replication and to promote virus assembly and budding via host UPP.