In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 5 ( 2023-5-24), p. e1011382-
Abstract:
Hepatitis B virus (HBV) chronically infects 296 million individuals and there is no cure. As an important step of viral life cycle, the mechanisms of HBV egress remain poorly elucidated. With proteomic approach to identify capsid protein (HBc) associated host factors and siRNA screen, we uncovered tumor susceptibility gene 101 (TSG101). Knockdown of TSG101 in HBV-producing cells, HBV-infected cells and HBV transgenic mice suppressed HBV release. Co-immunoprecipitation and site mutagenesis revealed that VFND motif in TSG101 and Lys-96 ubiquitination in HBc were essential for TSG101-HBc interaction. In vitro ubiquitination experiment demonstrated that UbcH6 and NEDD4 were potential E2 ubiquitin-conjugating enzyme and E3 ligase that catalyzed HBc ubiquitination, respectively. PPAY motif in HBc and Cys-867 in NEDD4 were required for HBc ubiquitination, TSG101-HBc interaction and HBV egress. Transmission electron microscopy confirmed that TSG101 or NEDD4 knockdown reduces HBV particles count in multivesicular bodies (MVBs). Our work indicates that TSG101 recognition for NEDD4 ubiquitylated HBc is critical for MVBs mediated HBV egress.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011382
DOI:
10.1371/journal.ppat.1011382.g001
DOI:
10.1371/journal.ppat.1011382.g002
DOI:
10.1371/journal.ppat.1011382.g003
DOI:
10.1371/journal.ppat.1011382.g004
DOI:
10.1371/journal.ppat.1011382.g005
DOI:
10.1371/journal.ppat.1011382.g006
DOI:
10.1371/journal.ppat.1011382.g007
DOI:
10.1371/journal.ppat.1011382.s001
DOI:
10.1371/journal.ppat.1011382.s002
DOI:
10.1371/journal.ppat.1011382.s003
DOI:
10.1371/journal.ppat.1011382.s004
DOI:
10.1371/journal.ppat.1011382.s005
DOI:
10.1371/journal.ppat.1011382.s006
DOI:
10.1371/journal.ppat.1011382.s007
DOI:
10.1371/journal.ppat.1011382.s008
DOI:
10.1371/journal.ppat.1011382.s009
DOI:
10.1371/journal.ppat.1011382.s010
DOI:
10.1371/journal.ppat.1011382.s011
DOI:
10.1371/journal.ppat.1011382.r001
DOI:
10.1371/journal.ppat.1011382.r002
DOI:
10.1371/journal.ppat.1011382.r003
DOI:
10.1371/journal.ppat.1011382.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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