Translational regulation by HIV leader RNA, TAT, and interferon-inducible enzymes.

Abstract

Every step in the replication cycle of HIV provides unique opportunities for controlling the progression of AIDS. In this regard, virus protein synthesis should be an important target for limiting HIV multiplication in cells. Molecular mechanisms in the regulation of HIV protein synthesis were therefore investigated in the context of interferon action. The interferon-inducible enzymes, 2-5A synthetase and dsRNA-dependent protein kinase, which can inhibit translation were activated by HIV-1 leader RNA. In cell-free systems, leader RNA and Tat protein of HIV inhibited and enhanced translation, respectively. An intriguing interplay of these viral and host factors were shown to influence the rate of translation in vitro. A model describing opposing actions of HIV Tat protein and interferon in HIV replication is represented.