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 type 1 (HIV-1) gag protein in ACH-2 cells was studied. The infectivity of HIV-1 from the cells stimulated with phorbol 12-myristate 13-acetate (PMA) was suppressed by pretreatment with N-myristoyl glycinal diethylacetal (N-Myr-GOA), a potent N-myristoylation inhibitor, and the blockage of myristoylation resulted in accumulation of immature gag precursors. 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 stimulated 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 the PMA-stimulated ACH-2, but no env was detected in the cells treated with N-Myr-GOA. Taken together, the results suggest that the myristoylation of HIV-1 gag seems to be responsible for both maturation of gag and acquisition of HIV-1 infectivity.
Furuishi
K
K
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Matsuoka
H
H
Takama
M
M
Takahashi
I
I
Misumi
S
S
Shoji
S
S
D000079:Acetaldehyde / Q000494:pharmacology*; D000080:Acetals / Q000494:pharmacology*; D002460:Cell Line; D003110:Colonic Neoplasms; D003673:Defective Viruses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D015683:Gene Products, gag / Q000378:metabolism*; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000080:Acetals; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D009227:Myristic Acids; D011498:Protein Precursors; D019814:Myristic Acid; C057591:N-myristoyl glycinal diethylacetal; D054303:HIV Reverse Transcriptase; D000079:Acetaldehyde; D013755:Tetradecanoylphorbol Acetate