In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 16, No. 12 ( 2020-12-14), p. e1009099-
Abstract:
Open reading frame (ORF) 45 is an outer tegument protein of Kaposi’s sarcoma-associated herpesvirus (KSHV). Genetic analysis of an ORF45-null mutant revealed that ORF45 plays a key role in the events leading to the release of KSHV particles. ORF45 associates with lipid rafts (LRs), which is responsible for the colocalization of viral particles with the trans-Golgi network and facilitates their release. In this study, we identified a host protein, RAB11 family interacting protein 5 (RAB11FIP5), that interacts with ORF45 in vitro and in vivo . RAB11FIP5 encodes a RAB11 effector protein that regulates endosomal trafficking. Overexpression of RAB11FIP5 in KSHV-infected cells decreased the expression level of ORF45 and inhibited the release of KSHV particles, as reflected by the significant reduction in the number of extracellular virions. In contrast, silencing endogenous RAB11FIP5 increased ORF45 expression and promoted the release of KSHV particles. We further showed that RAB11FIP5 mediates lysosomal degradation of ORF45, which impairs its ability to target LRs in the Golgi apparatus and inhibits ORF45-mediated colocalization of viral particles with the trans-Golgi network. Collectively, our results suggest that RAB11FIP5 enhances lysosome-dependent degradation of ORF45, which inhibits the release of KSHV particles, and have potential implications for virology and antiviral design.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009099
DOI:
10.1371/journal.ppat.1009099.g001
DOI:
10.1371/journal.ppat.1009099.g002
DOI:
10.1371/journal.ppat.1009099.g003
DOI:
10.1371/journal.ppat.1009099.g004
DOI:
10.1371/journal.ppat.1009099.g005
DOI:
10.1371/journal.ppat.1009099.g006
DOI:
10.1371/journal.ppat.1009099.g007
DOI:
10.1371/journal.ppat.1009099.g008
DOI:
10.1371/journal.ppat.1009099.g009
DOI:
10.1371/journal.ppat.1009099.t001
DOI:
10.1371/journal.ppat.1009099.s001
DOI:
10.1371/journal.ppat.1009099.s002
DOI:
10.1371/journal.ppat.1009099.s003
DOI:
10.1371/journal.ppat.1009099.s004
DOI:
10.1371/journal.ppat.1009099.s005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2205412-1
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