Role of the basic domain of human immunodeficiency virus type 1 matrix in macrophage infection.
The matrix domain of the human immunodeficiency virus type 1 (HIV-1) Gag protein contains a highly basic region near its amino terminus. It has been proposed that this basic domain, in conjunction with the HIV-1 accessory protein Vpr, is responsible for the localization of the HIV-1 preintegration complex to the nucleus in nondividing cells. It has also been postulated that the matrix basic domain assists in the targeting of the HIV-1 Gag precursor Pr55Gag to the plasma membrane during virus assembly. To evaluate the role of this highly basic sequence during infection of primary human monocyte-derived macrophages, single- and double-amino-acid-substitution mutations were introduced, and the effects on virus particle production, Gag protein processing, envelope glycoprotein incorporation into virus particles, and virus infectivity in the CEM(12D-7) T-cell line, peripheral blood mononuclear cells, and primary human monocyte-derived macrophages were analyzed. Although modest effects on virus particle production were observed with some of the mutants, none abolished infectivity in primary human monocyte-derived macrophages. In contrast with previously reported studies involving some of the same matrix basic domain mutants, infectivity in monocyte-derived macrophages was retained even when combined with a vpr mutation.
Freed
E O
EO
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
Englund
G
G
Martin
M A
MA
D000595:Amino Acid Sequence; D002460:Cell Line; D015683:Gene Products, gag / Q000235:genetics / Q000502:physiology*; D016336:Gene Products, vpr / Q000235:genetics; D015488:HIV Antigens / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation; D011499:Protein Processing, Post-Translational; D014764:Viral Proteins; D014771:Virion / Q000502:physiology; D014779:Virus Replication / Q000235:genetics; D054301:gag Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D016336:Gene Products, vpr; D015488:HIV Antigens; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; D054325:vpr Gene Products, Human Immunodeficiency Virus