SUSCEPTIBILITY OF HUMAN BONE-MARROW STROMAL CELLS TO HUMAN-IMMUNODEFICIENCY-VIRUS (HIV)

It is not known whether impaired hematopoiesis noted during human immu nodeficiency virus (HIV) infection results from infection of stem/prog enitor cells or of cells of the bone marrow microenvironment. Normal a dherent primary stromal layers were exposed to HIV to determine which of this mixture of endothelial cells, fibroblasts, and macrophages are susceptible to the virus. Viral p24 in supernatants was noted with mo nocytotropic HIV-1(Ada), HIV-1(Ba-L), and HIV-1(JR-FL) but not with ly mphotropic HIV-1(LAI) nor HIV-1(MN) strain, and only stromal macrophag es expressed the viral antigens. Coculture of the layers with PHA-acti vated normal lymphocytes failed to rescue lymphotropic virus. No p24 w as produced when macrophage-depleted stromal cells were exposed to eit her HIV-1(Ba-L) or HIV-1(LAI); proviral DNA was then amplified by PCR in cells exposed to either virus, though coculture with lymphocytes re scued only HIV-1(Ba-L). Altogether, these data indicate that macrophag es are the major targets of HIV in cultured stromal layers. As virus r eplication in macrophages did not affect the profile of major cytokine s involved in regulating hematopoiesis, HIV infection could alter hema topoiesis by other as yet unspecified mechanisms. (C) 1995 Academic Pr ess, Inc.