In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 6 ( 2022-6-17), p. e1010633-
Abstract:
Hepatitis B virus (HBV) has a highly restricted host range and cell tropism. Other than the human sodium taurocholate cotransporting polypeptide (huNTCP), the HBV entry receptor, host determinants of HBV susceptibility are poorly understood. Woodchucks are naturally infected with woodchuck hepatitis virus (WHV), closely related to HBV, but not with HBV. Here, we investigated the capabilities of woodchuck hepatic and human non-hepatic cell lines to support HBV infection. DNA transfection assays indicated that all cells tested supported both HBV and WHV replication steps post entry, including the viral covalently closed circular DNA (cccDNA) formation, which is essential for establishing and sustaining infection. Ectopic expression of huNTCP rendered one, but not the other, woodchuck hepatic cell line and the non-hepatic human cell line competent to support productive HBV entry, defined here by cccDNA formation during de novo infection. All huNTCP-expressing cell lines tested became susceptible to infection with hepatitis D virus (HDV) that shares the same entry receptor and initial steps of entry with HBV, suggesting that a late entry/trafficking step(s) of HBV infection was defective in one of the two woodchuck cell lines. In addition, the non-susceptible woodchuck hepatic cell line became susceptible to HBV after fusion with human hepatic cells, suggesting the lack of a host cell-dependent factor(s) in these cells. Comparative transcriptomic analysis of the two woodchuck cell lines revealed widespread differences in gene expression in multiple biological processes that may contribute to HBV infection. In conclusion, other than huNTCP, neither human- nor hepatocyte-specific factors are essential for productive HBV entry. Furthermore, a late trafficking step(s) during HBV infection, following the shared entry steps with HDV and before cccDNA formation, is subject to host cell regulation and thus, a host determinant of HBV infection.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010633
DOI:
10.1371/journal.ppat.1010633.g001
DOI:
10.1371/journal.ppat.1010633.g002
DOI:
10.1371/journal.ppat.1010633.g003
DOI:
10.1371/journal.ppat.1010633.g004
DOI:
10.1371/journal.ppat.1010633.g005
DOI:
10.1371/journal.ppat.1010633.g006
DOI:
10.1371/journal.ppat.1010633.g007
DOI:
10.1371/journal.ppat.1010633.s001
DOI:
10.1371/journal.ppat.1010633.s002
DOI:
10.1371/journal.ppat.1010633.s003
DOI:
10.1371/journal.ppat.1010633.s004
DOI:
10.1371/journal.ppat.1010633.s005
DOI:
10.1371/journal.ppat.1010633.s006
DOI:
10.1371/journal.ppat.1010633.s007
DOI:
10.1371/journal.ppat.1010633.s008
DOI:
10.1371/journal.ppat.1010633.s009
DOI:
10.1371/journal.ppat.1010633.s010
DOI:
10.1371/journal.ppat.1010633.s011
DOI:
10.1371/journal.ppat.1010633.s012
DOI:
10.1371/journal.ppat.1010633.s013
DOI:
10.1371/journal.ppat.1010633.s014
DOI:
10.1371/journal.ppat.1010633.s015
DOI:
10.1371/journal.ppat.1010633.s016
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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