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Productive human immunodeficiency virus-1 infection of megakaryocytic cells
is enhanced by tumor necrosis factor-alpha
D Monte, H Groux, B Raharinivo, B Plouvier, J Dewulf, T Clavel, C Grangette, G Torpier, C Auriault and A Capron
Centre d'Immunologie et de Biologie Parasitaire, Unite Mixte INSERM 167-
CNRS 624, Institut Pasteur de Lille, France.
Recent findings have indicated that megakaryocytes may be susceptible to
human immunodeficiency virus (HIV) infection, suggesting a potential role
for megakaryocytes as viral reservoirs in HIV-infected patients. We report
that the megakaryocytic cell line Dami could be productively infected with
the HTLV III-B strain of HIV-1, in 26 different experiments (results of 16
experiments are reported); productive infection lasted up to 30 weeks.
Despite a lack of detectable surface expression of the CD4 molecule and
very low levels of CD4 mRNA, between 40% and 60% of megakaryocytic cells
produced viral proteins after contact with HIV-1. Neither cytopathogenic
effects nor syncytial formation was observed. Production of high levels of
functional viral particles was indicated by analysis of p24 protein levels,
reverse transcriptase activity, ultrastructural studies, and the capacity
of supernatants from infected Dami cells to infect the Molt-4 T-
lymphocytic cell line. HIV-1 RNA and protein levels in infected Dami cells
were enhanced by treatment with tumor necrosis factor-alpha (TNF- alpha),
and decreased by treatment with interferon-alpha (IFN-alpha) and IFN-gamma.
Transient transfection of the megakaryocytic cells with various constructs
of the HIV-1 promoter (LTR) linked to the luciferase reporter gene
suggested that the effect of TNF-alpha was related, as in monocytic and
T-cell lines, to transactivation of the enhancer region of the HIV-1 LTR.
These findings indicate that signals provided by the immune system may
modulate HIV-1 expression in cells of the megakaryocytic lineage.
Volume 79,
Issue 10,
pp. 2670-2679,
05/15/1992
Copyright © 1992 by The American Society of Hematology

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