Important note: Information in this article was accurate in November 2002. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; November 11, 2002
Michael Greer, Senior Medical Writer
"The transcription factor NF-kappaB plays a central role in the human immunodeficiency virus type 1 (HIV-1) activation pathway. HIV-1 transcription is also regulated by protein acetylation," explained Vincent Quivy and colleagues at the Free University of Brussels and other institutions in Belgium, France, and the Netherlands.
A pair of agents that inhibit protein deacetylation can be used to disrupt the HIV latency process, preventing the virus from retreating to cellular reservoirs, Quivy and coauthors found.
The researchers assessed the utility of the deacetylase inhibitors trichostatin A (TSA) and sodium butyrate (NaBut). Both of these agents trigger transcriptional activity by the HIV long terminal repeat (LTR) promoter when used alone, they said.
Moreover, both TSA and NaBut combined synergistically with members of the NF-kappaB protein group to force LTR activity, study data showed. The combination of agents strongly prevented HIV from entering a latent state, ensuring that the virus would remain vulnerable to the effect of antiretroviral drugs.
The TSA-NaBut regimen worked by retarding the recovery of a cytoplasmic protein that suppresses NF-kappaB activity (Synergistic activation of human immunodeficiency virus type 1 promoter activity by NF-kappaB and inhibitors of deacetylases: potential perspectives for the development of therapeutic strategies. J Virol 2002 Nov;76(21):11091-103.
"The physiological relevance of the TNF-TSA (NaBut) synergism was shown on HIV-1 replication in both acutely and latently HIV-infected cell lines," Quivy and colleagues concluded. "Therefore, our results open new therapeutic strategies aimed at decreasing or eliminating the pool of latently HIV-infected reservoirs by forcing viral expression."
The corresponding author for this report is Carine van Lint, Universite Libre de Bruxelles, Institut de Biologie et de Medecine Moleculaires, Service de Chimie Biologique, Laboratoire de Virologie Moleculaire, rue des Profs Jeener et Brachet, 12, 6041 Gosselies, Belgium. E-mail: cvlint@ulb.ac.be.
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:
A pair of agents that inhibit protein deacetylation can be used to disrupt the HIV latency process
Trichostatin A and sodium butyrate combine synergistically with members of the NF-kappaB protein family to force viral transcriptional activity
These agents might therefore be useful for preventing HIV from going latent to hide from the effects of antiretroviral drugs
This article was prepared by AIDS Weekly editors from staff and other reports.
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