In:
PLOS Computational Biology, Public Library of Science (PLoS), Vol. 16, No. 11 ( 2020-11-5), p. e1008421-
Abstract:
Hepatitis C virus (HCV) causes acute hepatitis C and can lead to life-threatening complications if it becomes chronic. The HCV genome is a single plus strand of RNA. Its intracellular replication is a spatiotemporally coordinated process of RNA translation upon cell infection, RNA synthesis within a replication compartment, and virus particle production. While HCV is mainly transmitted via mature infectious virus particles, it has also been suggested that HCV-infected cells can secrete HCV RNA carrying exosomes that can infect cells in a receptor independent manner. In order to gain insight into these two routes of transmission, we developed a series of intracellular HCV replication models that include HCV RNA secretion and/or virus assembly and release. Fitting our models to in vitro data, in which cells were infected with HCV, suggests that initially most secreted HCV RNA derives from intracellular cytosolic plus-strand RNA, but subsequently secreted HCV RNA derives equally from the cytoplasm and the replication compartments. Furthermore, our model fits to the data suggest that the rate of virus assembly and release is limited by host cell resources. Including the effects of direct acting antivirals in our models, we found that in spite of decreasing intracellular HCV RNA and extracellular virus concentration, low level HCV RNA secretion may continue as long as intracellular RNA is available. This may possibly explain the presence of detectable levels of plasma HCV RNA at the end of treatment even in patients that ultimately attain a sustained virologic response.
Type of Medium:
Online Resource
ISSN:
1553-7358
DOI:
10.1371/journal.pcbi.1008421
DOI:
10.1371/journal.pcbi.1008421.g001
DOI:
10.1371/journal.pcbi.1008421.g002
DOI:
10.1371/journal.pcbi.1008421.g003
DOI:
10.1371/journal.pcbi.1008421.g004
DOI:
10.1371/journal.pcbi.1008421.g005
DOI:
10.1371/journal.pcbi.1008421.t001
DOI:
10.1371/journal.pcbi.1008421.t002
DOI:
10.1371/journal.pcbi.1008421.t003
DOI:
10.1371/journal.pcbi.1008421.t004
DOI:
10.1371/journal.pcbi.1008421.t005
DOI:
10.1371/journal.pcbi.1008421.t006
DOI:
10.1371/journal.pcbi.1008421.s001
DOI:
10.1371/journal.pcbi.1008421.s002
DOI:
10.1371/journal.pcbi.1008421.s003
DOI:
10.1371/journal.pcbi.1008421.s004
DOI:
10.1371/journal.pcbi.1008421.s005
DOI:
10.1371/journal.pcbi.1008421.s006
DOI:
10.1371/journal.pcbi.1008421.s007
DOI:
10.1371/journal.pcbi.1008421.s008
DOI:
10.1371/journal.pcbi.1008421.s009
DOI:
10.1371/journal.pcbi.1008421.s010
DOI:
10.1371/journal.pcbi.1008421.s011
DOI:
10.1371/journal.pcbi.1008421.s012
DOI:
10.1371/journal.pcbi.1008421.s013
DOI:
10.1371/journal.pcbi.1008421.s014
DOI:
10.1371/journal.pcbi.1008421.s015
DOI:
10.1371/journal.pcbi.1008421.s016
DOI:
10.1371/journal.pcbi.1008421.s017
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2193340-6
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