CD4-INDEPENDENT INFECTION OF HUMAN PERIPHERAL-BLOOD DENDRITIC CELLS WITH ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Dendritic cells (DC) are members of a distinct family of bone marrow-d erived leukocytes. DC are potent accessory cells for a number of T cel l-mediated immune responses, including autologous and allogeneic mixed leukocyte reactions, and mitogen- and antigen-stimulated lymphocyte p roliferation. In the present study, DC purified from human peripheral blood were inoculated with various strains (IIIB, SF2, WMJ1, SF162, 89 .6 and clone HXB2) of human immunodeficiency virus type 1 (HIV-1) disp laying different patterns of cellular tropism. Viral replication was d emonstrated by detection of p24 antigen (Ag) intracellularly and in cu lture supernatants, and by Southern and Northern blot analyses for the presence of HIV DNA and RNA, respectively, within infected cells. Cel l-free and cell-associated p24 Ag levels rose substantially when DC we re inoculated with strains SF162, 89.6 and clone HXB2. In contrast, p2 4 Ag levels rose only marginally after inoculation of DC with strains IIIB, SF2 and WMJ1. Purified DC did not express detectable membrane CD 4, although CD4 mRNA was detected by reverse transcriptase PCR. The pr esence of anti-CD4 monoclonal antibodies failed to block infection of DC by any of the HIV strains tested, suggesting the existence of a CD4 -independent alternative pathway of viral entry. The possibility that DC serve as a reservoir for HIV-1 must be considered.