Important note: Information in this article was accurate in February 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, February 1, 1999
Daniel J. DeNoon, Senior Editor
New studies suggest that taking away this key may be an effective antiviral strategy.
The trap is called the 2-5A/RNase L pathway. Viral infection activates this pathway, one of the major interferon-induced antiviral mechanisms. Viral infections produce double-stranded RNA structures that, like interferons, activate 2-5A-synthetase. Once activated this enzyme converts ATP into the odd series of oligomers known as 2-5A. 2-5A in turn activates a latent endoribonuclease which inhibits protein synthesis and inhibits viral replication.
Camille Martinand, Catherine Bisbal, and colleagues at the University of Montpellier, France, have cloned and characterized a polypeptide inhibitor of the 2-5A/RNase L pathway which they call RNase L inhibitor or RLI. They now show that RLI increases during the course of HIV infection.
Moreover, they showed that cell cultures transfected with cDNA encoding RLI antisense have a three-fold reduction in HIV viral load and a corresponding decrease in HIV RNA and HIV proteins.
"These results show that the 2-5A/RNase L pathway is potentially able to regulate HIV replication but is rapidly inhibited after the early stages of HIV infection," Martinand et al. wrote. "Altogether, these data suggest that RLI could be a cellular inhibitor induced by HIV-1 to inhibit the 2-5A/RNase L pathway."
They reported their findings in the Journal of Virology ("RNase L Inhibitor Is Induced during Human Immunodeficiency Virus Type 1 Infection and Down Regulates the 2-5A/RNase L Pathway in Human Cells," J Virol, 1999;73(1):290-6).
The authors suggested that new antiviral strategies could take advantage of this natural anti-HIV mechanism.
"The identification of the antagonistic pathways developed by viruses is important in understanding the physiopathology of viral infection and in the implementation of new and more efficient antiviral strategies," they wrote. "In particular, it would be of interest to understand how HIV-1 is able to induce RLI and to inhibit the cellular antiviral defenses."
This work was supported by grants from Institut National de la Sante et de la Recherche Medicale and from the Agence Nationale de la Recherche contre le SIDA.
The corresponding author for this study is Catherine Bisbal, Institut de Genetique Moleculaire de Montpellier, UMR 5535, CNRS- Universite de Montpellier II, 1919, route de Mende, 34293 Montpellier Cedex 5, France. Phone: 33-4-67-61-36-58. Fax: 33-4-67-04-02-45. Email: <bisbal@jones.igm.cnrs-mop.fr>.
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