Myristoylation of gag proteins of HIV-1 plays an important role in virus assembly.
The gag proteins of HIV-1 are modified by the addition of myristic acid to the amino terminal glycine residue. Site-directed mutagenesis was used to construct a mutant of HIV-1 in which this glycine residue was changed to an alanine. Upon transfection into cos-1 cells, the mutant genome directed the synthesis of the full complement of HIV-1 proteins, but p17 and p17-containing polyproteins were not myristoylated. The cells transfected with the mutant DNA did not release any virus particles and no viral cores were visible by electron microscopy. Furthermore, supernatant from these transfected cells failed to infect CEM cells. The expression and function of gp120 on the surface of cells transfected with the mutant DNA was unaffected as these cells formed syncytia comparable in both size and number to the ones obtained with wild-type DNA.
Department of Cell Biology, Advanced BioScience Laboratories, Inc., Kensington, Maryland 20895.
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Pal
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Reitz
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Tschachler
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Gallo
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Sarngadharan
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Veronese
D000595:Amino Acid Sequence; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D015488:HIV Antigens / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D015683:Gene Products, gag; D015488:HIV Antigens; D008051:Lipid Bilayers; D009227:Myristic Acids; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; D019814:Myristic Acid