A swine arterivirus deubiquitinase stabilizes two major envelope proteins and promotes production of viral progeny

Arteriviruses are enveloped positive-strand RNA viruses that assemble and egress using the host cell's exocytic pathway. In previous studies, we demonstrated that most arteriviruses use a unique -2 ribosomal frameshifting mechanism to produce a C-terminally modified variant of their nonstructur...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2021-03, Vol.17 (3), p.e1009403-e1009403
Main Authors: Guo, Rui, Yan, Xingyu, Li, Yanhua, Cui, Jin, Misra, Saurav, Firth, Andrew E, Snijder, Eric J, Fang, Ying
Format: Article
Language:English
Subjects:
Antibodies
Biology and Life Sciences
Coronaviruses
Fusion protein
Genetic aspects
Genomes
Health aspects
Hemorrhage
Hemorrhagic fever
L-Lactate dehydrogenase
Labeling
Lactate dehydrogenase
Lactic acid
Localization
Medicine and Health Sciences
Offspring
Peptides
Polyclonal antibodies
Progeny
Proteasomes
Proteins
Research and Analysis Methods
RNA viruses
Viral proteins
Virulence (Microbiology)
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Arteriviruses are enveloped positive-strand RNA viruses that assemble and egress using the host cell's exocytic pathway. In previous studies, we demonstrated that most arteriviruses use a unique -2 ribosomal frameshifting mechanism to produce a C-terminally modified variant of their nonstructural protein 2 (nsp2). Like full-length nsp2, the N-terminal domain of this frameshift product, nsp2TF, contains a papain-like protease (PLP2) that has deubiquitinating (DUB) activity, in addition to its role in proteolytic processing of replicase polyproteins. In cells infected with porcine reproductive and respiratory syndrome virus (PRRSV), nsp2TF localizes to compartments of the exocytic pathway, specifically endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and Golgi complex. Here, we show that nsp2TF interacts with the two major viral envelope proteins, the GP5 glycoprotein and membrane (M) protein, which drive the key process of arterivirus assembly and budding. The PRRSV GP5 and M proteins were found to be poly-ubiquitinated, both in an expression system and in cells infected with an nsp2TF-deficient mutant virus. In contrast, ubiquitinated GP5 and M proteins did not accumulate in cells infected with the wild-type, nsp2TF-expressing virus. Further analysis implicated the DUB activity of the nsp2TF PLP2 domain in deconjugation of ubiquitin from GP5/M proteins, thus antagonizing proteasomal degradation of these key viral structural proteins. Our findings suggest that nsp2TF is targeted to the exocytic pathway to reduce proteasome-driven turnover of GP5/M proteins, thus promoting the formation of GP5-M dimers that are critical for arterivirus assembly.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1009403