title: SUMO1 depletion prevents lipid droplet accumulation and HCV replication.
abstract: Infection by hepatitis C virus (HCV) is a major public-health problem. Chronic infection often leads to cirrhosis, steatosis, and hepatocellular carcinoma. The life cycle of HCV depends on the host cell machinery and involves intimate interaction between viral and host proteins. However, the role of host proteins in the life cycle of HCV remains poorly understood. Here, we identify the small ubiquitin-related modifier (SUMO1) as a key host factor required for HCV replication. We performed a series of cell biology and biochemistry experiments using the HCV JFH-1 (Japanese fulminate hepatitis 1) genotype 2a strain, which produces infectious particles and recapitulates all the steps of the HCV life cycle. We observed that SUMO1 is upregulated in Huh7.5 infected cells. Reciprocally, SUMO1 was found to regulate the expression of viral core protein. Moreover, knockdown of SUMO1 using specific siRNA influenced the accumulation of lipid droplets and reduced HCV replication as measured by qRT-PCR. Thus, we identify SUMO1 as a key host factor required for HCV replication. To our knowledge, this is the first report showing that SUMO1 regulates lipid droplets in the context of viral infection. Our report provides a meaningful insight into how HCV replicates and interacts with host proteins and is of significant importance for the field of HCV and RNA viruses.
authors.affiliation: INSERM, UMR-S 785, 94800, Villejuif, France. abdellah.akil@u-psud.fr.|Univ Paris-Sud, 91400, Orsay, France. abdellah.akil@u-psud.fr.|Faculty of Science, UFR Biochemistry-Immunology, Univ Mohammed V, Rabat-Agdal, Morocco. abdellah.akil@u-psud.fr.
authors.forename: Abdellah
authors.initials: A
authors.lastname: Akil
authors.affiliation: Univ Paris-Sud, 91400, Orsay, France.
authors.forename: Ghaith
authors.initials: G
authors.lastname: Wedeh
authors.affiliation: INSERM, UMR-S 785, 94800, Villejuif, France.|Univ Paris-Sud, 91400, Orsay, France.|Centre for Advanced Studies in Vaccinology and Biotechnology (CASVAB), University of Balochistan, Quetta, Pakistan.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Zahid Mustafa
authors.affiliation: INSERM, UMR-S 785, 94800, Villejuif, France.
authors.forename: Ama
authors.initials: A
authors.lastname: Gassama-Diagne
mesh_terms: D002460:Cell Line; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000172:deficiency* / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D034741:RNA, Small Interfering; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D014758:Viral Core Proteins
keywords: HCV; Lipid droplets; SUMO1