MiniReview: Antiviral Targets Series, Number 1

The impetus to generate effective but safe compounds to combat the acquired immune deficiency syndrome (AIDS) has been hastened by the increasing incidence of human immunodeficiency virus (HIV) infection. With the toxicities associated with zidovudine (AZl), research has also focused on other potential targets for antiviral therapy. Viral replication occurs through reverse transcription and an obligatory DNA intermediate which integrates into the host chromosome to generate a provirus. Translation of particular mRNAs generates polyproteins which must undergo processing through limited proteolysis to generate the functional or active forms of the constituent viral proteins. The proteinase that is responsible for carrying out specific cleavages within the gag (p56) or gag-pol (p160) precursors to release the multiple functional elements therein (Fig. 1) is itself encoded within the viral genome and is therefore an intrinsic component of the polyprotein. _ In HIV, the proteinase is encoded within the pol open reading frame (ORF). In contrast, in other retroviruses such as Rous sarcoma virus or avian sarcoma/leukosis virus (RSV) and avian myeloblastosis associated virus (MAV), it is contained wholly within the gag region so that, in these cases, proteinase is produced in equivalent amounts to the other gag proteins. Without the intervention of this proteolytic activity, non-infectious viral particles are produced. Such proteinases, particularly in the case of HIV, are therefore very attractive targets for antiviral chemotherapy.