title: The promiscuous CC chemokine receptor D6 is a functional coreceptor for primary isolates of human immunodeficiency virus type 1 (HIV-1) and HIV-2 on astrocytes.
abstract: The role of coreceptors other than CCR5 and CXCR4 in the pathogenesis of human immunodeficiency virus (HIV) disease is controversial. Here we show that a promiscuous CC chemokine receptor, D6, can function as a coreceptor for various primary dual-tropic isolates of HIV type 1 (HIV-1) and HIV-2. Furthermore, D6 usage is common among chimeric HIV-1 constructs bearing the gp120 proteins of isolates from early seroconverting patients. D6 mRNA and immunoreactivity were demonstrated to be expressed in HIV-1 target cells such as macrophages, peripheral blood mononuclear cells, and primary astrocytes. In primary astrocytes, an RNA interference-mediated knockdown of D6 expression inhibited D6-tropic isolate infection. D6 usage may account for some previous observations of alternative receptor tropism for primary human cells. Thus, D6 may be an important receptor for HIV pathogenesis in the brain and for the early dissemination of virus in the host.
authors: Wohl Virion Centre, Division of Infection and Immunity, University College London, UK.
authors: Stuart J D
authors: SJ
authors: Neil
authors: Marlen M I
authors: MM
authors: Aasa-Chapman
authors: Paul R
authors: PR
authors: Clapham
authors: Robert J
authors: RJ
authors: Nibbs
authors: Aine
authors: A
authors: McKnight
authors: Robin A
authors: RA
authors: Weiss
mesh_terms: D001253:Astrocytes / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D015497:HIV-1 / Q000502:physiology*; D015498:HIV-2 / Q000502:physiology*; D006801:Humans; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000378:metabolism / Q000502:physiology*; D011991:Receptors, Virus / Q000378:metabolism / Q000502:physiology*; D014779:Virus Replication
chemical_list: C106311:CCR6 protein, human; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D011991:Receptors, Virus