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Journal of Virology, August 2005, p. 9618-9624, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.9618-9624.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

Wohl Virion Centre, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, United Kingdom,¹ Program in Molecular Medicine, University of Massachusetts, Worcester, Massachusetts,² Cancer Research UK Beaston Laboratories, Garscube Estate, Switchback Rd., Glasgow, United Kingdom³

Received 4 January 2005/ Accepted 7 April 2005

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.

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