title: Hepatitis C virus core protein enhances HIV-1 replication in human macrophages through TLR2, JNK, and MEK1/2-dependent upregulation of TNF-α and IL-6.
abstract: Despite their differential cell tropisms, HIV-1 and HCV dramatically influence disease progression in coinfected patients. Macrophages are important target cells of HIV-1. We hypothesized that secreted HCV core protein might modulate HIV-1 replication. We demonstrate that HCV core significantly enhances HIV-1 replication in human macrophages by upregulating TNF-α and IL-6 via TLR2-, JNK-, and MEK1/2-dependent pathways. Furthermore, we show that TNF-α and IL-6 secreted from HCV core-treated macrophages reactivates monocytic U1 cells latently infected with HIV-1. Our studies reveal a previously unrecognized role of HCV core by enhancing HIV-1 infection in macrophages.
authors.affiliation: Microbiology and Immunology Graduate Program, Drexel University College of Medicine, Philadelphia, PA 19102, USA; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
authors.forename: Gokul
authors.initials: G
authors.lastname: Swaminathan
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA; Master of Science in Forensic Science Program, Professional Studies in the Health Sciences, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pascual
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA; Master of Interdisciplinary Health Sciences Program, Professional Studies in the Health Sciences, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
authors.forename: Germaine
authors.initials: G
authors.lastname: Rival
authors.affiliation: Microbiology and Immunology Graduate Program, Drexel University College of Medicine, Philadelphia, PA 19102, USA; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
authors.forename: Renzo
authors.initials: R
authors.lastname: Perales-Linares
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA; Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
authors.forename: Julio
authors.initials: J
authors.lastname: Martin-Garcia
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA; Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA. Electronic address: sonia.navas-martin@drexelmed.edu.
authors.forename: Sonia
authors.initials: S
authors.lastname: Navas-Martin
mesh_terms: D060085:Coinfection / Q000821:virology; D057809:HEK293 Cells; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006526:Hepatitis C / Q000821:virology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000821:virology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D014758:Viral Core Proteins / Q000502:physiology*; D014779:Virus Replication
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; C495342:TLR2 protein, human; C439524:TNF protein, human; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D020930:MAP Kinase Kinase Kinases
keywords: HIV-1; Hepatitis C virus core protein; Interleukin 6; MAPK kinase; Macrophages; Toll-like receptor 2; Tumor necrosis factor alpha