RRC ID 73121
Author Shirasago Y, Fukazawa H, Nagase S, Shimizu Y, Mizukami T, Wakita T, Suzuki T, Tani H, Kondoh M, Kuroda T, Yasuda S, Sato Y, Hanada K, Fukasawa M.
Title A single mutation in the E2 glycoprotein of hepatitis C virus broadens the claudin specificity for its infection.
Journal Sci Rep
Abstract Entry of the hepatitis C virus (HCV) into host cells is a multistep process mediated by several host factors, including a tight junction protein claudin-1 (CLDN1). We repeatedly passaged HCV-JFH1-tau, an HCV substrain with higher infectivity, on Huh7.5.1-8 cells. A multi-passaged HCV-JFH1-tau lot was infectious to CLDN1-defective S7-A cells, non-permissive to original HCV-JFH1-tau infection. We identified a single mutation, M706L, in the E2 glycoprotein of the HCV-JFH1-tau lot as an essential mutation for infectivity to S7-A cells. The pseudovirus JFH1/M706L mutant could not infect human embryonic kidney 293 T (HEK293T) cells lacking CLDN family but infected HEK293T cells expressing CLDN1, CLDN6, or CLDN9. Thus, this mutant virus could utilize CLDN1, and other CLDN6 and CLDN9, making HCV possible to infect cells other than hepatocytes. iPS cells, one of the stem cells, do not express CLDN1 but express CLDN6 and other host factors required for HCV infection. We confirmed that the HCV-JFH1-tau-derived mutant with an M706L mutation infected iPS cells in a CLDN6-dependent manner. These results demonstrated that a missense mutation in E2 could broaden the CLDN member specificity for HCV infection. HCV may change its receptor requirement through a single amino acid mutation and infect non-hepatic cells.
Volume 12(1)
Pages 20243
Published 2022-11-24
DOI 10.1038/s41598-022-23824-3
PII 10.1038/s41598-022-23824-3
PMID 36424447
PMC PMC9691748
MeSH Claudin-1* / genetics HEK293 Cells Hepacivirus* / genetics Hepatitis C* / genetics Humans Mutation, Missense Viral Envelope Proteins* / genetics
IF 3.998
Human and Animal Cells 253G1(HPS0002)