AIDSWEEKLY Plus; November 25, 2002
Michael Greer, Senior Medical Writer

"The immunosuppressive macrolide rapamycin is used in humans to prevent graft rejection," explained Jocelyn Roy and colleagues at the University Hospital Complex of Quebec and the University of Laval in St. Foy. "This drug acts by selectively repressing the translation of proteins that are encoded by an mRNA bearing a 5'-polypyrimidine tract (e.g., ribosomal proteins, elongation factors)."

Rapamycin also selectively impairs HIV mRNA transcription, preventing the virus from efficiently replicating, Roy and coauthors found.

HIV transcription was suppressed in infected human T lymphoid cells and peripheral blood lymphocytes after rapamycin treatment, while cells infected with non-HIV gene vectors were unaffected by the immunosuppressant, the researchers reported. Rapamycin completely prevented the production of infectious viral particles from cells infected with either X4- or R5-tropic strains of HIV.

Expression of the HIV long terminal repeat (LTR) promoter gene was significantly inhibited by rapamycin, study data showed. The results of further experiments suggested that rapamycin "is primarily affecting the life cycle of HIV-1 at a transcriptional level."

The second exon of the gene coding for HIV's transactivation protein Tat contains a polypyrimidine motif (The immunosuppressant rapamycin represses human immunodeficiency virus type 1 replication. Antimicrob Agents Chemother 2002 Nov;46(11):3447-55.

"Northern blot analysis confirmed that this compound is selectively targeting HIV-1 mRNA synthesis," Roy and colleagues concluded.

The corresponding author for this report is Michel J. Tremblay, Laboratoire d'Immuno-Retrovirologie Humaine, Centre de Recherche en Infectiologie, RC709 Hopital CHUL, Centre Hospitalier Universitaire de Quebec 2705 Boul. Laurier, St. Foy, Quebec, G1V 4G2, Canada. E-mail: michel.j.tremblay@crchul.ulaval.ca.

A search at www.NewsRx.net using the search term "AIDS and HIV therapy" yielded 1193 articles in 29 specialized reports.

Key points reported in this study include:

• The immunosuppressive macrolide rapamycin inhibits HIV replication

• Rapamycin disrupts critical viral transcriptional activity

• The immunosuppressant completely prevented production of infectious viral particles from cells infected with X4- or R5-tropic HIV strains

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Roy J, Paquette JS, Fortin JF, et al., "The immunosuppressant rapamycin represses human immunodeficiency virus type 1 replication", Antimicrob Agents Chemother 2002 Nov;46(11):3447-55.

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