Human immunodeficiency virus type 1-induced hematopoietic inhibition is independent of productive infection of progenitor cells in vivo

Human immunodeficiency virus (HIV)-infected individuals exhibit a variety o f hematopoietic dysfunctions. The SCID-hu mouse (severe combined immunodefi cient mouse transplanted with human fetal thymus and liver tissues) can be used to model the loss of human hematopoietic precursor cell function follo wing HN infection and has a distinct advantage in that data can be obtained in the absence of confounding factors often seen in infected humans. In th is study, we establish that HIV type 1 (HIV-1) bearing a reporter gene inse rted into the viral vpr gene is highly aggressive in depleting human myeloi d and erythroid colony-forming precursor activity in vivo. Human CD34(+) pr ogenitor cells can be efficiently recovered from infected implants yet do n ot express the viral reporter gene, despite severe functional defects. Our results indicate that HIV-1 infection alone leads to hematopoietic inhibiti on in vivo; however, this effect is due to indirect mechanisms rather than to direct infection of CD34(+) cells in vivo.