LC3B is not recruited along with the autophagy elongation complex (ATG5-12/16L1) at HCV replication site and is dispensable for viral replication

Autor:	Marwa Khabir, Matthieu Blanchet, Patrick Labonté, Ahmed Fahmy
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	0301 basic medicine Autophagosome RNA viruses Physiology Autophagy-Related Proteins lcsh:Medicine Proximity ligation assay Hepacivirus Viral Nonstructural Proteins Biochemistry Autophagy-Related Protein 5 chemistry.chemical_compound Immune Physiology lcsh:Science Pathology and laboratory medicine Multidisciplinary Immune System Proteins Cell Death Chemistry Hepatitis C virus Viral Replication Complex Medical microbiology Hepatitis C 3. Good health Cell biology Cell Processes Viruses Host-Pathogen Interactions Pathogens Microtubule-Associated Proteins Research Article Autophagic Cell Death ATG5 Immunology RNA-dependent RNA polymerase Viral Structure Microbiology Antibodies 03 medical and health sciences Virology Humans Protein Interactions NS5B Medicine and health sciences 030102 biochemistry & molecular biology Flaviviruses Autophagy lcsh:R Organisms Viral pathogens Autophagosomes Biology and Life Sciences Proteins Cell Biology RNA-Dependent RNA Polymerase Viral Replication Hepatitis viruses Microbial pathogens 030104 developmental biology Viral replication Viral replication complex lcsh:Q
Zdroj:	PLoS ONE, Vol 13, Iss 10, p e0205189 (2018) PLoS ONE
ISSN:	1932-6203
Popis:	Hepatitis C virus (HCV) infection is known to induce autophagosome accumulation as observed by the typical punctate cytoplasmic distribution of LC3B-II in infected cells. Previously, we showed that viral RNA-dependent RNA polymerase (NS5B) interacts with ATG5, a major component of the autophagy elongation complex that is involved in the formation of double-membrane vesicles (DMV), and demonstrated that the autophagy elongation complex (ATG5-12/16L1) but not LC3B is required for proper membranous web formation. In this study, the colocalization and in situ interaction of all HCV replicase components with the constituent of the autophagy elongation complex and LC3B were analyzed. The results clearly show the recruitment of the elongation complex to the site of viral replication. Using in situ proximity ligation assay, we show that ATG5, but not ATG16L1, interacts with several HCV replicase components suggesting that the recruitment is directed via the ATG5-12 conjugate. Interestingly, no E3-like conjugation activity of ATG5-12/16L1 can be detected at the at HCV replication site since LC3B-II is not found along with the elongation complex at the site of viral replication. In agreement with this result, no sign of in situ interaction of LC3B with the replicase components is observed. Finally, using dominant negative forms of ATG proteins, we demonstrate that ATG5-12 conjugate, but not LC3-II formation, is critical for viral replication. Altogether, these findings suggest that although HCV needs the elongation complex for its replication, it has developed a mechanism to avoid canonical LC3-II accumulation at viral replication site.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e19a6cc20f5734864b4efeb1b263e7b8 http://europepmc.org/articles/PMC6171931?pdf=render Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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