J. Virol., Aug 1997, 5713-5722, Vol 71, No. 8
SG Kitchen, CH Uittenbogaart and JA Zack
Human immunodeficiency virus (HIV) infection of the thymus could have
profound effects on development of the immune response, particularly in
children. We and others have established that in addition to infecting and
depleting CD4-bearing thymocytes, functional HIV proviruses are found in
thymocytes lacking surface CD4 expression. Using in vitro thymocyte
cultures, we show that neither HIV-mediated down regulation of CD4 nor
CD4-independent infection contributes to the localization of HIV in cells
lacking the primary virus receptor. Rather, infection of a CD4-positive
precursor cell (CD4 positive/CD8 positive) with subsequent differentiation
into a mature CD4-negative phenotype results in productively infected
CD4-negative cells. This novel mechanism may contribute to pathogenesis by
distributing viral sequences into functional subsets of T cells typically
refractory to HIV infection and could account for the presence of viral DNA
in CD8-positive lymphocytes recently observed in patients.
Copyright © 1997, American Society for Microbiology
Mechanism of human immunodeficiency virus type 1 localization in CD4- negative thymocytes: differentiation from a CD4-positive precursor allows productive infection
Department of Microbiology and Immunology, University of California Los Angeles School of Medicine, 90095, USA.
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