Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo

Mycophenolic acid, a selective inhibitor of the de novo synthesis of guanosine nucleotides in T and B lymphocytes, has been proposed to inhibit human immunodeficiency virus (HIV) replication in vitro by depleting the substrate (guanosine nucleotides) for reverse transcriptase. Here we show that myco...

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Vydáno v:	Nature medicine Ročník 6; číslo 7; s. 762 - 768
Hlavní autoři:	Chapuis, Aude G., Paolo Rizzardi, G., D'Agostino, Claudia, Attinger, Antoine, Knabenhans, Christian, Fleury, Sylvain, Acha-Orbea, Hans, Pantaleo, Giuseppe
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.07.2000 Nature Publishing Group
Témata:	Anti-HIV Agents - therapeutic use Apoptosis Biomedical and Life Sciences Biomedicine Cancer Research CD4 antigen CD4-Positive T-Lymphocytes - drug effects CD8 antigen CD8-Positive T-Lymphocytes - drug effects Dose-Response Relationship, Drug HIV Infections - drug therapy Human immunodeficiency virus 1 Humans Immunosuppressive Agents - pharmacology Immunosuppressive Agents - therapeutic use Infectious Diseases Lymphocyte Activation - drug effects Lymphocytes Metabolic Diseases Molecular Medicine mycophenolic acid Mycophenolic Acid - analogs & derivatives Mycophenolic Acid - pharmacology Mycophenolic Acid - therapeutic use Neurosciences T-Lymphocytes - drug effects
ISSN:	1078-8956, 1546-170X
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Shrnutí:	Mycophenolic acid, a selective inhibitor of the de novo synthesis of guanosine nucleotides in T and B lymphocytes, has been proposed to inhibit human immunodeficiency virus (HIV) replication in vitro by depleting the substrate (guanosine nucleotides) for reverse transcriptase. Here we show that mycophenolic acid induced apoptosis and cell death in a large proportion of activated CD4 + T cells, thus indicating that it may inhibit HIV infection in vitro by both virological mechanisms and immunological mechanisms (depletion of the pool of activated CD4 + T lymphocytes). Administration of mycophenolate mophetil, the ester derivate of mycophenolic acid, to HIV-infected subjects treated with anti-retroviral therapy and with undetectable viremia resulted in the reduction of the number of dividing CD4 + and CD8 + T cells and in the inhibition of virus isolation from purified CD4 + T-cell populations. Based on these results, the potential use of mycophenolate mophetil in the treatment of HIV infection deserves further investigation in controlled clinical trials.
Bibliografie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 content type line 23
ISSN:	1078-8956 1546-170X
DOI:	10.1038/77489