title: HIV-1 Nef interacts with HCV Core, recruits TRAF2, TRAF5 and TRAF6, and stimulates HIV-1 replication in macrophages.
abstract: Tumor necrosis factor receptor-associated factor (TRAF) signaling plays a central role in many biological activities, such as the regulation of immune and inflammatory responses and control of apoptosis, which are key events in the pathogenesis of the human immunodeficiency virus (HIV)-1 and the hepatitis C virus (HCV) infections. Here we show that TRAF2, TRAF5 and TRAF6 interact with the HIV-1 Nef protein, an immunomodulatory viral protein expressed and released by cells infected by the virus. We also found that TRAF2 and TRAF5 interact with the HCV Core protein. Interestingly, we observed that HIV-1 Nef interacts with HCV Core. The activation of TRAF (2, 5, 6) - mediated by HIV-1 Nef and HCV Core - enhanced the activation of the nuclear factor-kappa B (NF-κB) and increased HIV-1 replication in monocyte- derived macrophages (MDMs). The knockdown of TRAF2, TRAF5 and TRAF6 resulted in decreased NF-κB activation and reduced HIV-1 replication in MDMs. Our results reveal a mechanism by which the activation of the TRAF pathway by HIV-1 Nef and HCV Core favors the replication of HIV-1 in macrophages and could be a critical factor for optimal replication of HIV-1 in macrophages of HIV-HCV-coinfected patients.
authors.affiliation: Department of Virology, UPRES EA4266 Pathogens and Inflammation, SFR FED 4234, University of Franche-Comte, CHU Besançon, Besançon, France.
authors.forename: Kashif A
authors.initials: KA
authors.lastname: Khan
authors.forename: Wasim
authors.initials: W
authors.lastname: Abbas
authors.forename: Audrey
authors.initials: A
authors.lastname: Varin
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.forename: Vincent
authors.initials: V
authors.lastname: Di Martino
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dichamp
authors.forename: Georges
authors.initials: G
authors.lastname: Herbein
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D005434:Flow Cytometry; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000821:virology; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics / Q000378:metabolism*; D048015:TNF Receptor-Associated Factor 5 / Q000235:genetics / Q000378:metabolism*; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D047992:TNF Receptor-Associated Factor 2; D048015:TNF Receptor-Associated Factor 5; D048029:TNF Receptor-Associated Factor 6; D014758:Viral Core Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C069130:nucleocapsid protein, Hepatitis C virus