IMPORTANCE OF RIBOSOMAL FRAMESHIFTING FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PARTICLE ASSEMBLY AND REPLICATION

The recent development and use of protease inhibitors have demonstrate d the essential role that combination therapy will play in the treatme nt of individuals infected with the human immunodeficiency virus type 1 (HIV-1). Past clinical experience suggests that due to the appearanc e of resistant HIV-1 variants, additional therapeutics will be require d in the future. To identify new options for combination therapy, it i s of paramount importance to pursue novel targets for drug development . Ribosomal frameshifting is one potential target that has not been fu lly explored. Data presented here demonstrate that small molecules can stimulate frameshifting, leading to an imbalance in the ratio of Gag to Gag Pol and inhibiting HIV-1 replication at what appears to be the point of viral particle assembly. Thus, we propose that frameshifting represents a new target for the identification of novel anti-HIV-1 the rapeutics.