Mutations in the N-terminal region of human immunodeficiency virus type 1 matrix protein block intracellular transport of the Gag precursor.
The matrix domain of human immunodeficiency virus type 1 Gag polyprotein was studied for its role in virus assembly. Deletion and substitution mutations caused a dramatic reduction in virus production. Mutant Gag polyproteins were myristoylated and had a high affinity for membrane association. Immunofluorescence staining revealed a large accumulation of mutant Gag precursors in the cytoplasm, while wild-type Gag proteins were primarily associated with the cell surface membrane. These results suggest a defect in intracellular transport of the mutant Gag precursors. Thus, in addition to myristoylation, the N-terminal region of the matrix domain is involved in determining Gag protein transport to the plasma membrane. Wild-type Gag polyproteins interacted with and efficiently packaged mutant Gag into virions. This finding is consistent with the hypothesis that intermolecular interaction of Gag polyproteins might occur in the cytoplasm prior to being transported to the assembly site on the plasma membrane.
Yuan
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Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115.
Yu
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Lee
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Essex
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D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport; D002451:Cell Compartmentation; D005455:Fluorescent Antibody Technique; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D015488:HIV Antigens / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015488:HIV Antigens; D009838:Oligodeoxyribonucleotides; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1