title: Macrophages are the major target cell for HIV infection in long-term marrow culture and demonstrate dual susceptibility to lymphocytotropic and monocytotropic strains of HIV-1.
abstract: Haematological abnormalities are often seen in patients infected with HIV. A number of mechanisms are thought to contribute to this bone marrow suppression, including impaired stromal function and direct infection of progenitor cells. Evidence suggests that both bone marrow progenitor cells and perhaps stromal cells are open to infection by HIV, which raises the possibility that bone marrow stromal cells may serve as a reservoir for HIV. This study investigated the cellular targets and kinetics of in vitro infection of stroma in long-term bone marrow culture (LTBMC) using both mono- and lymphocytotropic strains of HIV-1. p24 ELISA and reverse transcriptase (RT) assay demonstrated that stroma could be infected with HIV and release infectious virions. The target cells for infection were shown to be macrophages by immunohistochemistry (APAAP), dual immunofluorescence staining (using CD68 and p24) and electron microscopy. The data show that it was possible to infect stroma in LTBMC with HIV and that such infection was productive. The main target for infection was bone marrow macrophages. In contrast to peripheral blood derived macrophages, these cells were susceptible to both lymphocytotropic and monocytotropic strains of HIV-1. The data suggests that these bone marrow macrophages may act as a reservoir for HIV, Infection of bone marrow macrophages may affect haemopoiesis either by transmission of HIV infection to developing progenitor cells through direct cell-to-cell contact or by altering the ability of the stroma to support normal development.
authors.affiliation: Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, London.
authors.forename: V
authors.initials: V
authors.lastname: Gill
authors.forename: R J
authors.initials: RJ
authors.lastname: Shattock
authors.forename: A R
authors.initials: AR
authors.lastname: Freeman
authors.forename: G
authors.initials: G
authors.lastname: Robinson
authors.forename: G E
authors.initials: GE
authors.lastname: Griffin
authors.forename: E C
authors.initials: EC
authors.lastname: Gordon-Smith
authors.forename: F M
authors.initials: FM
authors.lastname: Gibson
mesh_terms: D001853:Bone Marrow / Q000821:virology*; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000821:virology*; D008854:Microscopy, Electron; D017154:Stromal Cells / Q000821:virology; D013997:Time Factors; D018523:Tropism