MECHANISM OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 LOCALIZATION IN CD4-NEGATIVE THYMOCYTES - DIFFERENTIATION FROM A CD4-POSITIVE PRECURSOR ALLOWS PRODUCTIVE INFECTION

Human immunodeficiency virus (HN) infection of the thymus could have p rofound effects on development of the immune response, particularly in children. We and others have established that in addition to infectin g and depleting CD4-bearing thymocytes, functional HIV proviruses are found in thymocytes lacking surface CD4 expression. Using in vitro thy mocyte cultures, we show that neither HIV-mediated down regulation of CD4 nor CD4-independent infection contributes to the localization of H IV in cells lacking the primary virus receptor. Rather, infection of a CD4-positive precursor cell (CD4 positive/CD8 positive) with subseque nt differentiation into a mature CD4-negative phenotype results in pro ductively infected CD4-negative cells. This novel mechanism may contri bute to pathogenesis by distributing viral sequences into functional s ubsets of T cells typically refractory to HIV infection and could acco unt for the presence of viral DNA in CDS-positive lymphocytes recently observed in patients.