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Inhibition of Human T-Cell Protein Blocks HIV Replication

Novel therapeutic target could circumvent problem of viral drug resistance

TUESDAY, April 29 (HealthDay News) -- Inhibition of a T-cell protein that is required for T-cell activation blocks HIV replication in in vitro experiments, according to an article published online April 28 in the Proceedings of the National Academy of the Sciences Early Edition.

Julie A. Readinger, Ph.D., of the National Institutes of Health in Bethesda, Md., and colleagues explored whether inhibition of inducible T-cell kinase (ITK), a human protein that regulates T-cell activation, affected HIV infection and replication. The researchers used a chemical ITK inhibitor as well as RNA interference to inactivate ITK in cultures of human T cells, and then exposed the cells to HIV-1 viruses.

Inhibition of ITK partially blocked HIV viral entry and affected multiple steps of HIV replication, resulting in marked reductions in intracellular p24 levels after infection and decreased virus spread within the culture, the investigators found. In contrast, overexpression of ITK led to increased viral transcription and virus-like particle formation, the researchers report.

"Current treatment of HIV relies on antiretroviral agents that are subject to the development of resistant viruses. Because inhibitors directed against cellular proteins required for HIV replication may be less prone to this problem, the use of such inhibitors is of growing interest," the authors write.

The study authors disclose that a patent for ITK has been filed.

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