BLOCKAGE OF N-MYRISTOYLATION OF HIV-1 GAG INDUCES THE PRODUCTION OF IMPOTENT PROGENY VIRUS

The role of the N-myristoylation of the human immunodeficiency virus t ype 1 (HIV-1) gag protein in ACH-2 cells was studied. The infectivity of HIV-1 from the cells stimulated with phorbol Ig-myristate 13-acetat e (PMA) was suppressed by pretreatment with N-myristoyl glycinal dieth ylacetal (N-Myr-GOA), a potent N-myristoylation inhibitor, and the blo ckage of myristoylation resulted in accumulation of immature gag precu rsors. The viral particles which budded from the non-N-Myr-GOA-treated ACH-2 cells stimulated with PMA exhibited a typical viral phenotype, whereas those which budded from the N-Myr-GOA-treated ACH-2 cells stim ulated with PMA were twisted, as observed electron microscopically. In electron microscopic analyses with gold-labeled monoclonal antibodies to gag and env, gag and env were detected adjacent to each other in t he PMA-stimulated ACH-2, but no env was detected in the cells treated with N-Myr-GOA. Taken together, the results suggest that the myristoyl ation of HIV-1 gag seems to be responsible for both maturation of gag and acquisition of HIV-1 infectivity. (C) 1997 Academic Press.