JVI Accepts, published online ahead of print on 3 October 2007

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J. Virol. doi:10.1128/JVI.00976-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Dendritic Cells Are Less Susceptible to HIV-2 Than HIV-1 Infection

Melody G. Duvall, Karin Loré, Hetty Blaak, David A. Ambrozak, William C. Adams, Kathlyn Santos, Christof Geldmacher, John R. Mascola, Andrew J. McMichael, Hilton C. Whittle, Sarah L. Rowland-Jones, and Richard A. Koup^*

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Virology, Erasmus MC, Rotterdam, The Netherlands; Immunology Laboratory, BSL-3 Core Virology Laboratory, Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA; MRC Laboratories Fajara, P.O. Box 273 Banjul, The Gambia, West Africa

^* To whom correspondence should be addressed. Email: rkoup{at}mail.nih.gov.

HIV-1 infection of dendritic cells (DCs) has been documented in vivo, and may be an important contributor to HIV-1 transmission and pathogenesis. HIV-1-specific CD4⁺ T cells respond to HIV antigens presented by HIV-1-infected DCs and in this process become infected, thereby providing a mechanism through which HIV-1-specific CD4⁺ T cells could become preferentially infected in vivo. HIV-2 disease is attenuated with respect to HIV-1 and host immune responses are thought to be contributory. Here, we investigated the susceptibility of primary myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) to infection by HIV-2. We found that neither CCR5-tropic primary HIV-2 isolates nor a lab-adapted CXCR4-tropic HIV-2 could efficiently infect mDCs or pDCs, though these viruses could infect primary CD4⁺ T cells in vitro. HIV-2-exposed mDCs were also incapable of transferring virus to autologous CD4⁺ T cells. Despite this, we found that HIV-2-specific CD4⁺ T cells contained more viral DNA than memory CD4⁺ T cells of other specificities in vivo. These data suggest that either infection of DCs is not an important contributor to infection of HIV-2-specific CD4⁺ T cells in vivo, or that infection of DCs by HIV-2 occurs at a level undetectable in vitro. The frequent carriage of HIV-2 DNA within HIV-2-specific CD4⁺ T cells, however, does not appear to be incompatible with preserved numbers and functionality of HIV-2-specific CD4⁺ T cells in vivo, suggesting that additional mechanisms contribute to maintenance of HIV-2-specific CD4⁺ T cell help in vivo.