title: Dendritic cells are less susceptible to human immunodeficiency virus type 2 (HIV-2) infection than to HIV-1 infection.
abstract: Human immunodeficiency virus type 1 (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 disease, 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 strain 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 that is 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.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.
authors.forename: Melody G
authors.initials: MG
authors.lastname: Duvall
authors.forename: Karin
authors.initials: K
authors.lastname: Loré
authors.forename: Hetty
authors.initials: H
authors.lastname: Blaak
authors.forename: David A
authors.initials: DA
authors.lastname: Ambrozak
authors.forename: William C
authors.initials: WC
authors.lastname: Adams
authors.forename: Kathlyn
authors.initials: K
authors.lastname: Santos
authors.forename: Christof
authors.initials: C
authors.lastname: Geldmacher
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Assan
authors.initials: A
authors.lastname: Jaye
authors.forename: Hilton C
authors.initials: HC
authors.lastname: Whittle
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
mesh_terms: D017951:Antigen Presentation; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002454:Cell Differentiation; D018920:Coculture Techniques; D004279:DNA, Viral / Q000032:analysis / Q000302:isolation & purification; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000821:virology*; D005434:Flow Cytometry; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D015498:HIV-2 / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D016133:Polymerase Chain Reaction
chemical_list: D004279:DNA, Viral