Novel compound inhibits HIV replication in cell cultures, suggesting possible new type of AIDS drug

Philadelphia, Pa. A compound that inhibits human immunodeficiency virus (HIV) in human immune system cells may eventually provide a new therapeutic approach against AIDS by blocking HIV infection at an early stage. It may also deny the virus a hiding place in the cells from which HIV infection commonly rebounds when current AIDS medications are interrupted.

A research team led by pediatric immunologists at The Childrens Hospital of Philadelphia announced its results in the March 27 Proceedings of the National Academy of Sciences. The research, by Steven D. Douglas, M.D., Jian-Ping Lai, M.D., and Wen-Zhe Ho, M.D., was carried out in human cell cultures.

The compound, CP-96,345, binds to receptors on the surface of monocyte-derived macrophages (MDM), which are immune system cells. These macrophages play an important role in HIV infection because they are a reservoir for the virus. HIV infection remains latent in these cells even while the anti-HIV drug cocktail, highly active antitretroviral therapy, controls the active infection. If the drug cocktail is halted, HIV infection surges back.

"This compound is potentially a very powerful therapy because it may close the door to the virus," said Dr. Douglas, the chief of Immunology at Childrens Hospital and lead author of the article. CP-96,345 interrupts the process by which particular strains of HIV, the R5 strains, enter macrophages through receptors on the macrophages cell surface. Many AIDS researchers are targeting those specific receptors, CCR5 receptors, as a way to block HIV infection in its early stages.

Crucial to the action of CP-96,345 is a naturally produced protein called substance P. First discovered in 1930, substance P is a neurotransmitter, a chemical that carries signals within the brain and elsewhere in the nervous system. Known to be an active transmitter of pain signals, substance P also plays an important role, still under investigation, in the immune system. In 1997, Drs. Doug

Contact: John Ascenzi
Children's Hospital of Philadelphia

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