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Upregulation of human immunodeficiency virus-1 in chronically infected
monocytic cell line by both contact with endothelial cells and cytokines
ST Fan, K Hsia and TS Edgington
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Cells of monocytic lineage (Mo) persistently infected with human
immunodeficiency virus (HIV) have been suspected to be a major reservoir
for in vivo transmission of virus to susceptible target cells. Cellular
events and mechanisms that upregulate viral gene expression in such cells
are important issues. Because the traffic of such cells is central to
biodistribution of HIV, we have explored the impact of interaction of
endothelium with HIV-1-infected U1 promonocytic cells. Coculturing of U1
with human umbilical endothelial cells (HUVEC) for 24 to 72 hours in the
absence of stimulation induced HIV-1 p24 biosynthesis significantly.
Antibody-blocking experiments indicated that CD11/CD18 integrins play a
role in upregulation of HIV expression elicited by interaction with HUVEC.
Engagement of CD11b/CD18 by adherence of U1 to surfaces coated with either
the cognate ligand fibrinogen or monoclonal antibody specific for
CD11b/CD18 also enhanced p24 biosynthesis. Furthermore, endothelial cells
were found to constitutively synthesize and secrete soluble factors that
enhanced HIV- 1 synthesis. The enhancing factors, of estimated size 10 to
45 kD, were induced in HUVEC to high levels by monokines or by
lipopolysaccharide, resulting in markedly enhanced HIV-1 expression by U1.
These endothelial cell-derived HIV-1-enhancing factors consist of, among
others, interleukin-6 (IL-6), IL-1 beta, and granulocyte-macrophage CSF
(GM-CSF). Our results suggest that activation of HIV biosynthesis in
infected Mo via interaction with endothelium may impact significantly on
the tissue distribution and pathogenesis of HIV infections.
Volume 84,
Issue 5,
pp. 1567-1572,
09/01/1994
Copyright © 1994 by The American Society of Hematology

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