MECHANISM OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 LOCALIZATION IN CD4-NEGATIVE THYMOCYTES - DIFFERENTIATION FROM A CD4-POSITIVE PRECURSOR ALLOWS PRODUCTIVE INFECTION
Sg. Kitchen et al., MECHANISM OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 LOCALIZATION IN CD4-NEGATIVE THYMOCYTES - DIFFERENTIATION FROM A CD4-POSITIVE PRECURSOR ALLOWS PRODUCTIVE INFECTION, Journal of virology, 71(8), 1997, pp. 5713-5722
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.