Open AccessInduction of selective autophagy in cells replicating hepatitis C virus genome
Author(s) -
Haruhiko Mori,
Takasuke Fukuhara,
Chikako Ono,
Tomokazu Tamura,
Asuka Sato,
Yuzy Fauzyah,
Masami Wada,
Tomoyoshi Okamoto,
Takeshi Noda,
Tamotsu Yoshimori,
Yoshiharu Matsuura
Publication year - 2018
Publication title -
journal of general virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.55
H-Index - 167
eISSN - 1465-2099
pISSN - 0022-1317
DOI - 10.1099/jgv.0.001161
Subject(s) - autophagy , atg5 , biology , virology , hepatitis c virus , viral replication , bafilomycin , infectivity , virus , microbiology and biotechnology , biochemistry , apoptosis
Hepatitis C virus (HCV) infection is known to induce autophagy, but the mechanism of autophagy induced by HCV remains controversial. Here, we investigated the characteristics of autophagy induced by HCV infection. First, to examine the involvement of autophagy-related gene (ATG) proteins in HCV-induced LC3 lipidation, we established ATG5, ATG13 or ATG14 knockout (KO) Huh7.5.1 cell lines and confirmed that the accumulation of lipidated LC3 was induced in an ATG13- and ATG14-independent manner. On the other hand, HCV infectivity was not influenced by deficiencies in these genes. We also confirmed that LC3-positive dots were co-localized with ubiquitinated aggregates, and deficiency of ATG5 or ATG14 enhanced the accumulation of ubiquitinated aggregates compared to that in the restored cells, suggesting that HCV infection induces ATG5- and ATG14-dependent selective autophagy. Moreover, LC3-positive ubiquitinated aggregates accumulated near the site of the replication complex. We further examined autophagy flux in cells replicating HCV RNA using bafilomycin or E64d, and found that the increase of LC3 lipidation by treatment with bafilomycin or E64d was impaired in HCV-replicating cells, suggesting that autophagy flux is inhibited by the progress of HCV infection. Our present study suggests that (1) HCV RNA replication induces selective autophagy and (2) the progress of HCV infection impairs autophagy flux.