PMID- 28931085
OWN - NLM
STAT- MEDLINE
DCOM- 20171017
LR  - 20181113
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 13
IP  - 9
DP  - 2017 Sep
TI  - HCV-induced autophagosomes are generated via homotypic fusion of phagophores that 
      mediate HCV RNA replication.
PG  - e1006609
LID - 10.1371/journal.ppat.1006609 [doi]
LID - e1006609
AB  - Hepatitis C virus (HCV) induces autophagy to promote its replication, including 
      its RNA replication, which can take place on double-membrane vesicles known as 
      autophagosomes. However, how HCV induces the biogenesis of autophagosomes and how 
      HCV RNA replication complex may be assembled on autophagosomes were largely 
      unknown. During autophagy, crescent membrane structures known as phagophores 
      first appear in the cytoplasm, which then progress to become autophagosomes. By 
      conducting electron microscopy and in vitro membrane fusion assay, we found that 
      phagophores induced by HCV underwent homotypic fusion to generate autophagosomes 
      in a process dependent on the SNARE protein syntaxin 7 (STX7). Further analyses 
      by live-cell imaging and fluorescence microscopy indicated that HCV-induced 
      phagophores originated from the endoplasmic reticulum (ER). Interestingly, 
      comparing with autophagy induced by nutrient starvation, the progression of 
      phagophores to autophagosomes induced by HCV took significantly longer time, 
      indicating fundamental differences in the biogenesis of autophagosomes induced by 
      these two different stimuli. As the knockdown of STX7 to inhibit the formation of 
      autophagosomes did not affect HCV RNA replication, and purified phagophores could 
      mediate HCV RNA replication, the assembly of the HCV RNA replication complex on 
      autophagosomes apparently took place during the formative stage of phagophores. 
      These findings provided important information for understanding how HCV 
      controlled and modified this important cellular pathway for its own replication.
FAU - Wang, Linya
AU  - Wang L
AD  - Department of Molecular Microbiology and Immunology, University of Southern 
      California, Keck School of Medicine, Los Angeles, California, United States of 
      America.
FAU - Kim, Ja Yeon
AU  - Kim JY
AD  - Department of Molecular Microbiology and Immunology, University of Southern 
      California, Keck School of Medicine, Los Angeles, California, United States of 
      America.
FAU - Liu, Helene Minyi
AU  - Liu HM
AD  - Institute of Biochemistry and Molecular Biology, College of Medicine, National 
      Taiwan University, Taipei, Taiwan.
FAU - Lai, Michael M C
AU  - Lai MMC
AUID- ORCID: 0000-0002-5206-9451
AD  - Department of Molecular Microbiology and Immunology, University of Southern 
      California, Keck School of Medicine, Los Angeles, California, United States of 
      America.
AD  - Research Center for Emerging Viruses, China Medical University Hospital and China 
      Medical University, Taichung, Taiwan.
FAU - Ou, Jing-Hsiung James
AU  - Ou JJ
AUID- ORCID: 0000-0002-8274-5705
AD  - Department of Molecular Microbiology and Immunology, University of Southern 
      California, Keck School of Medicine, Los Angeles, California, United States of 
      America.
LA  - eng
GR  - R01 DK094652/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20170919
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Autophagosomes/*virology
MH  - Autophagy/*physiology
MH  - Cell Line
MH  - Hepacivirus/*physiology
MH  - Hepatitis C/*virology
MH  - Humans
MH  - Microscopy, Electron, Transmission
MH  - RNA, Viral/*biosynthesis
MH  - Virus Replication/*physiology
PMC - PMC5621699
COIS- The authors have declared that no competing interests exist.
EDAT- 2017/09/21 06:00
MHDA- 2017/10/19 06:00
PMCR- 2017/09/19
CRDT- 2017/09/21 06:00
PHST- 2017/06/14 00:00 [received]
PHST- 2017/08/26 00:00 [accepted]
PHST- 2017/09/29 00:00 [revised]
PHST- 2017/09/21 06:00 [pubmed]
PHST- 2017/10/19 06:00 [medline]
PHST- 2017/09/21 06:00 [entrez]
PHST- 2017/09/19 00:00 [pmc-release]
AID - PPATHOGENS-D-17-01269 [pii]
AID - 10.1371/journal.ppat.1006609 [doi]
PST - epublish
SO  - PLoS Pathog. 2017 Sep 19;13(9):e1006609. doi: 10.1371/journal.ppat.1006609. 
      eCollection 2017 Sep.