Oncogene Science, Inc., 106 Charles Lindbergh Blvd., Uniondale, NY 11553

Received 6/2/97; Accepted 6/4/97

2. INTRODUCTION

HIV-1, the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS), displays a complex regulation of viral gene expression during its life cycle. Unlike many "simple" retroviruses (i.e. avian and murine leukemia viruses), which express only three viral genes, the genome of HIV-1 encodes nine genes whose expression patterns are tightly regulated during the HIV-1 replication cycle (Figure 1, for reviews see 1, 2, 3). In the infected host cell, HIV expresses over 20 distinct mRNA species (reviewed in 4). The early stage of regulation of the HIV-1 life cycle is marked by the appearance of the viral regulatory molecules Tat, Rev, and Nef, encoded by the fully spliced 2 kb class of viral mRNAs. The late viral life cycle gene expression is characterized by the cytoplasmic appearance of the 4 kb class of single spliced and 9.2 kb unspliced mRNAs, that encode the proteins required for the assembly of infectious virions. The viral transactivator Rev allows this transition into the late cycle (5, 6), and is therefore essential for viral replication. In effect, proviral mutants that do not express Rev fail to produce structural proteins and therefore cannot form new infectious viral particles (5, 7).

Figure 1. Schematic representation of the HIV-1 genome. Gag-pol and Envelope (gp 160) are the classical retroviral proteins. Note the overlapping reading frames. In addition to these structural proteins and enzymes, HIV has a number of accessory proteins that have crucial function in the replication cycle and pathogenesis: Tat, Rev, Nef, Vif, Vpr and Vpu. Rev is expressed very early in the life cycle, and is the product of a fully spliced mRNA

Because of its essential role in HIV replication, Rev constitutes an excellent target for therapeutic intervention. Its mode of action and specific interactions with its target RNA and cellular proteins have been extensively studied and elegantly elucidated, and this body of knowledge adds to the attractiveness of Rev as a target. The purpose of this article is to briefly review the latest developments on Rev, and how this knowledge can be used for development of anti-viral strategies, as well as to review current efforts in this field.