Sommerfelt MA, Hunter E; Symposium on Nonhuman Primate Models for AIDS.
J Med Primatol. 1992 Feb-May; 21: 37 (abstract no. 18).
University of Alabama at Birmingham, Dept. of Microbiology, Birmingham, AL. 35294.
The MPMV protease is defined as an aspartyl protease and is responsible for cleavage of structural gene precursor proteins either during or shortly after budding in the process of maturation. The MPMV transmembrane (TM) envelope glycoprotein is initially cleaved from the Pr86 envelope precursor by a Golgi endopeptidase as a 22kD cell-associated molecule (gp22). This is cleaved in the cytoplasmic domain to the gp20 glycoprotein found on released virions. We have made two mutations in the MPMV genome that inactivate viral protease activity and result in the release of non-infectious, immature particles. Interestingly, gp22 remains uncleaved in these particles, demonstrating that the viral protease is responsible for this proteolysis event. We have also shown that synthetic peptides designed to inhibit the HIV protease will inhibit MPMV protease activity in a dose dependent manner. The cleavage of gp22(TM) to gp20 appears to be more sensitive to inhibition than gag precursor protein cleavage. The infectivity of particles treated with increasing concentrations of inhibitor show that as for HIV particles there is negligible reverse transcriptase (RT) activity until day 10 post-infection. Extending this assay until day 22 shows a delayed increase in RT activity related to the levels of inhibitor the virions were exposed to. This raises the possibility that the effect of these inhibitors is reversible in this system; alternatively the delayed detection of virus reverse transcriptase may reflect a small fraction of infectious virus that escapes the effects of inhibitor. Experiments to differentiate between these possibilities will be reported.
Publication Types:
Keywords:
- Aspartic Endopeptidases
- Endopeptidases
- Gene Products, gag
- Glycoproteins
- HIV Protease
- HIV Protease Inhibitors
- Mason-Pfizer monkey virus
- Peptides
- Pharmaceutical Preparations
- RNA-Directed DNA Polymerase
- Virion
Other ID:
UI: 102181598
From Meeting Abstracts