title: Human immunodeficiency virus enhances hepatitis C virus replication by differential regulation of IFN and TGF family genes.
abstract: HIV co-infection significantly impacts the natural history of hepatitis C virus (HCV) by increasing plasma HCV viral load, accelerating liver disease progression, and reducing rates of HCV clearance. Cytokines play an important role in regulating hepatic inflammation and fibrogenesis during chronic HCV infection, yet the impact of HIV on cytokine expression is unknown. In this study, an HCV continuous infection cell culture system was modified to permit co-infection with HIV to test the hypothesis that virus-induced disregulation of immune-response genes, particularly interferons and TGF-β, may create a permissive environment for the initial establishment of HIV/HCV co-infection in the host. CCR5-expressing Huh-7.5 hepatoma cells were transduced with human CD4 antigen to allow HIV infection in vitro. Co-infection of CD4⁺ Huh-7.5 cells with HIV and HCV or co-culture of HIV-infected CD4⁺ Huh-7.5 cells and HCV-infected Huh-7.5 cells increased the level of HCV RNA compared to HCV mono-infection. Quantitative gene expression analysis revealed HIV-induced up regulation of most tested IFN family genes when compared to HCV or co-infection. HCV infection induced up regulation of many TGF family genes that were subsequently down-regulated in the presence of HIV or HIV/HCV. Interestingly, co-infection resulted in down regulation of several IFN genes and significant up regulation of TGF-β genes leading to an overall enhancement of HCV replication. These data suggest that HIV infection may influence HCV replication in vitro by increasing levels of HCV RNA, possibly through the differential regulation of endogenous IFN and TGF family genes.
authors: Immunopathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors: Xiaozhen
authors: X
authors: Zhang
authors: Marybeth
authors: M
authors: Daucher
authors: Josue
authors: J
authors: Baeza
authors: Cheol-Woo
authors: CW
authors: Kim
authors: Rodney
authors: R
authors: Russell
authors: Shyamasundaran
authors: S
authors: Kottilil
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D060085:Coinfection / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000502:physiology*; D016174:Hepacivirus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism; D007372:Interferons / Q000502:physiology*; D019713:Receptors, CCR5 / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome; D015291:Transforming Growth Factors / Q000502:physiology*; D014779:Virus Replication
chemical_list: D015704:CD4 Antigens; D007155:Immunologic Factors; D019713:Receptors, CCR5; D015291:Transforming Growth Factors; D007372:Interferons