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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Published in:Nature medicine Vol. 6; no. 7; pp. 762 - 768
Main Authors: Chapuis, Aude G., Paolo Rizzardi, G., D'Agostino, Claudia, Attinger, Antoine, Knabenhans, Christian, Fleury, Sylvain, Acha-Orbea, Hans, Pantaleo, Giuseppe
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.07.2000
Nature Publishing Group
Subjects:
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
Online Access:Get full text
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Summary: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.
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ISSN:1078-8956
1546-170X
DOI:10.1038/77489