The gag proteins of human immunodeficiency virus type 1: mechanisms of virus assembly and possibilities for interference.

Abstract

Using two different experimental systems we were able to define two distinct regions in the sequence of gag proteins of HIV which function in the assembly of structural components of the virus and particle morphogenesis. Since assembly could be inhibited by addition of synthetic non-toxic peptide compounds, a new group of antiviral agents may be developed. This approach represents a completely new inhibitory principle. Besides irreversibly blocking the synthesis of progeny virus, this class of peptidomimetic inhibitors might be of special interest since non-infectious particles are released which should still be capable of stimulating the immune system and helping to induce an improved immune status. Those effects have been observed when mice were vaccinated with Rauscher murine leukemia virus and treated simultaneously with zidovudine and interferon-α [69]. Besides the development of antiviral compounds active viral protein regions actively involved in morphogenesis may be developed for applications in gene therapy using assembly defective gag proteins to negatively influence virus production via transdominant-negative effects.