HIV-1 Rev function as target for antiretroviral drug development.
OBJECTIVE
One of the major problems in HIV chemotherapy is appearance of drug-resistant virus strains. Novel HIV intervention strategies are required and new targets must be considered. The nuclear export of intron-containing HIV-1 mRNA is an essential step in the viral replication cycle and is a prospective antiviral target. This nucleocytoplasmic transport is mediated by the viral protein Rev. Rev binds as a multimeric complex to the viral mRNA and exports it to the cytoplasm exploiting the CRM1-mediated cellular machinery. Inhibitors acting on the interface between virus and cell could overcome the problems of drug resistance against virus-specific treatments. These drugs have an added value in combination therapy as they are expected to be less prone to virus-drug resistance selection, but they are likely to be more cytotoxic.


RESULTS
We will discuss the therapeutic approaches aimed at interfering with Rev function, both now and likely in the future, and the recent attempts that have been undertaken to design small molecules against this target.


CONCLUSIONS
Recent approaches provide leads for development of new compounds. A better understanding of the mechanism of Rev action and its interaction with the cellular transport pathway is required to identify and rationally design novel strategies that may have potential for future antiretroviral intervention.
Rega Institute for Medical Research, 3000 Lewen, Belgium. dirk.daelemans@rega.kuleuven.be
Dirk
D
Daelemans
Christophe
C
Pannecouque