INFECTION OF ACCESSORY DENDRITIC CELLS BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Many details of the pathogenesis of the human immunodeficiency virus type 1 remain to be elucidated. Details of how the virus gains entry via the mucosal surface upon sexual contact or during breast feeding remain obscure. The means by which the infection travels throughout the body as well as the nature of the major reservoirs of virus infection remains, for the most part, unknown. Recent studies raise the possibility that cells of the Langerhans/dendritic lineage play a central role in human immunodeficiency virus (HIV-1) infection and pathogenesis. It has been known for several years that veiled dendritic cells in the circulation as well as skin Langerhans are infected in people with prolonged HIV-1 infections. More recently it has been found that a large burden of viral DNA sequences is found, not only in the circulating T-cell population, but also in a population that is defined as a non-T, non-B, non-monocyte/macrophage population rich in T-helper dendritic cells. Detailed analysis of infection of primary blood-derived T-helper dendritic cells by HIV-1 shows that such cells are the most susceptible cells in the blood to infection by this virus. The cells also produce much more virus per cell than do purified populations of other blood mononuclear cells. Moreover, primary blood-derived T-helper dendritic cells are not killed by infection by HIV-1. These cells are susceptible to lymphotropic, monocyte tropic, and primary isolates of HIV-1. The sensitivity of primary blood-derived T-helper dendritic cells to infection by HIV-1 has been shown to be attributable to rapid uptake of virus particles as well as rapid synthesis of viral DNA. Subsequent steps of virus replication also occur more rapidly and more efficiently in populations of primary blood-derived T-helper dendritic cells than they do in purified preparations of blood-derived T cells and monocyte/macrophages. Studies with primates using the simian immunodeficiency virus (SIV) show that dendritic cells at the surface of sexual mucosa are rapidly infected upon exposure to high concentrations of the virus. SIV is also produced in abundance in Langerhans cells located at the surface of the sexual mucosa in animals infected for prolonged periods of time.