Protein tyrosyl phosphatases in T cell activation: implication for human immunodeficiency virus transcriptional activity.

The protein tyrosine phosphatases (PTPs) superfamily is a large group of enzymes showing a wide diversity of structure and biological functions. Their implication in the regulation of signal transduction processes is critical for homeostasis and efficient cellular activation. Disturbance of the delicate balance between protein tyrosine kinase and protein tyrosine phosphatase activities is at the heart of a large number of diseases. Control of cellular activation is especially important for human immunodeficiency virus type 1 (HIV-1) since this retrovirus requires activated T cells in order to replicate efficiently. Identification of PTPs implicated in signaling pathways leading to upregulation of HIV-1 gene transcription therefore contributes to the general understanding of cellular factors needed for strong HIV-1 replication and progression to AIDS. The use of bisperoxovanadium compounds as potent, specific, and highly purified PTP inhibitors releases HIV-1 from PTP control and strongly increases HIV-1 gene expression. These inhibitors can thus be used to study signal transduction mechanisms regulated by PTP activity that are important for HIV-1 replication and provide new and interesting therapeutic avenues for the efficient control of this debilitating retroviral infection.