In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 7 ( 2021-7-23), p. e1009746-
Abstract:
HCV cell-culture system uses hepatoma-derived cell lines for efficient virus propagation. Tumor cells cultured in glucose undergo active aerobic glycolysis, but switch to oxidative phosphorylation for energy production when cultured in galactose. Here, we investigated whether modulation of glycolysis in hepatocytes affects HCV infection. We showed HCV release, but not entry, genome replication or virion assembly, is significantly blocked when cells are cultured in galactose, leading to accumulation of intracellular infectious virions within multivesicular body (MVB). Blockade of the MVB-lysosome fusion or treatment with pro-inflammatory cytokines promotes HCV release in galactose. Furthermore, we found this glycometabolic regulation of HCV release is mediated by MAPK-p38 phosphorylation. Finally, we showed HCV cell-to-cell transmission is not affected by glycometabolism, suggesting that HCV cell-to-supernatant release and cell-to-cell transmission are two mechanistically distinct pathways. In summary, we demonstrated glycometabolism regulates the efficiency and route of HCV release. We proposed HCV may exploit the metabolic state in hepatocytes to favor its spread through the cell-to-cell transmission in vivo to evade immune response.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009746
DOI:
10.1371/journal.ppat.1009746.g001
DOI:
10.1371/journal.ppat.1009746.g002
DOI:
10.1371/journal.ppat.1009746.g003
DOI:
10.1371/journal.ppat.1009746.g004
DOI:
10.1371/journal.ppat.1009746.g005
DOI:
10.1371/journal.ppat.1009746.g006
DOI:
10.1371/journal.ppat.1009746.g007
DOI:
10.1371/journal.ppat.1009746.s001
DOI:
10.1371/journal.ppat.1009746.s002
DOI:
10.1371/journal.ppat.1009746.s003
DOI:
10.1371/journal.ppat.1009746.s004
DOI:
10.1371/journal.ppat.1009746.s005
DOI:
10.1371/journal.ppat.1009746.s006
DOI:
10.1371/journal.ppat.1009746.s007
DOI:
10.1371/journal.ppat.1009746.s008
DOI:
10.1371/journal.ppat.1009746.s009
DOI:
10.1371/journal.ppat.1009746.s010
DOI:
10.1371/journal.ppat.1009746.r001
DOI:
10.1371/journal.ppat.1009746.r002
DOI:
10.1371/journal.ppat.1009746.r003
DOI:
10.1371/journal.ppat.1009746.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
Permalink