Blocking T-Cell Enzyme Slows Spread of HIV

AIDS researchers have found that blocking a key T-cell enzyme inhibited the ability of HIV viruses to enter host cells and hijack their mechanisms for protein synthesis.

The HIV virus mutates rapidly, generating strains that become immune to most available antiretroviral drugs. The use of multi-drug regimens or rapid switching of drugs can increase the risk of toxic side effects, be difficult for patients to follow, and are not always successful. Therefore, considerable efforts are now being made to develop drugs that target host cell proteins that are required by HIV.

Investigators at the [U.S.] National Institutes of Health (Bethesda, MD, USA) focused their attention on the T-cell enzyme interleukin-2-inducible T cell kinase (ITK), a Tec family tyrosine kinase that is an important regulator of T cell activation. Since productive infection of T cells with HIV requires T cell activation, the investigators studied how ITK affects HIV infection by using ITK-specific siRNA, a kinase-inactive ITK mutant, or an ITK inhibitor.

Results published in the April 28, 2008, online edition of the Proceedings of the [U.S.] National Academy of Sciences (PNAS) revealed that loss of ITK function resulted in marked reductions in intracellular levels of the HIV p24 antigen. Loss of ITK function after establishment of HIV infection also decreased virus spread within the culture. ITK was required for efficient transcription of HIV proteins, and overexpression of ITK increased both viral transcription and virus-like particle formation.

"We were pleased and excited to realize the outcome of our approach,” said senior author Dr. Pamela Schwartzberg, a senior investigator at NIH. "Suppression of the ITK protein caused many of the pathways that HIV uses to be less active, thereby inhibiting or slowing HIV replication. There are several companies who have published research about ITK inhibitors as part of their target program. We hope that others will extend our findings and that ITK inhibitors will be pursued as HIV therapies.”


Related Links:
National Institutes of Health