title: HIV-1 Nef is transferred from expressing T cells to hepatocytic cells through conduits and enhances HCV replication.
abstract: HIV-1 infection enhances HCV replication and as a consequence accelerates HCV-mediated hepatocellular carcinoma (HCC). However, the precise molecular mechanism by which this takes place is currently unknown. Our data showed that infectious HIV-1 failed to replicate in human hepatocytic cell lines. No discernible virus replication was observed, even when the cell lines transfected with HIV-1 proviral DNA were co-cultured with Jurkat T cells, indicating that the problem of liver deterioration in the co-infected patient is not due to the replication of HIV-1 in the hepatocytes of the HCV infected host. Instead, HIV-1 Nef protein was transferred from nef-expressing T cells to hepatocytic cells through conduits, wherein up to 16% (average 10%) of the cells harbored the transferred Nef, when the hepatocytic cells were co-cultured with nef-expressing Jurkat cells for 24 h. Further, Nef altered the size and numbers of lipid droplets (LD), and consistently up-regulated HCV replication by 1.5∼2.5 fold in the target subgenomic replicon cells, which is remarkable in relation to the initially indolent viral replication. Nef also dramatically augmented reactive oxygen species (ROS) production and enhanced ethanol-mediated up-regulation of HCV replication so as to accelerate HCC. Taken together, these data indicate that HIV-1 Nef is a critical element in accelerating progression of liver pathogenesis via enhancing HCV replication and coordinating modulation of key intra- and extra-cellular molecules for liver decay.
authors.affiliation: Department of Cell Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas, United States of America; Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: In-Woo
authors.initials: IW
authors.lastname: Park
authors.affiliation: Department of Cell Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas, United States of America; Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Cell Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas, United States of America; Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Luo
authors.affiliation: Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, United States of America.
authors.forename: Myoung-Gwi
authors.initials: MG
authors.lastname: Ryou
authors.affiliation: Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Linden
authors.initials: L
authors.lastname: Green
authors.affiliation: Department of Cell Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas, United States of America; Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Johnny J
authors.initials: JJ
authors.lastname: He
mesh_terms: D002460:Cell Line; D018920:Coculture Techniques; D060085:Coinfection; D017930:Genes, Reporter; D015658:HIV Infections; D015497:HIV-1; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1