Inhibition of viral assembly in murine cells by HIV-1 matrix.
In human cells, the N-terminal matrix (MA) domain of the human immunodeficiency virus type 1 (HIV-1) Gag targets assembly to specific membrane compartments. In murine fibroblasts, membrane targeting of Gag and assembly of HIV-1 are inefficient. These deficiencies are relieved by replacement of HIV-1 MA with murine leukemia virus (MLV) MA in chimeric proviruses. In this study, we examined chimeric HIV-1 carrying tandem MLV and HIV-1 MA domains and found that the addition of MLV MA to the N-terminus of HIV-1 Gag enhanced membrane binding in murine cells, but was not sufficient to stimulate virus production. Removal of HIV MA was required to observe more efficient Gag processing and increased virus production in murine cells. Deletion of the globular head of MA also alleviated the blocks to membrane binding and Gag processing in murine cells, yet did not lead to increased virus production. These MA-dependent, cell-type-specific phenotypes suggest that host factors interact with the globular head of MA to regulate membrane binding and additional membrane-independent step(s) required for assembly.
Hübner
Wolfgang
W
Department of Pharmacology and Biological Chemistry, Center for Immunobiology, Mount Sinai School of Medicine, One Gustave Levy Place Box 1215, New York, NY 10029, USA.
Chen
Benjamin K
BK
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D002678:Chimera; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D015683:Gene Products, gag / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D015488:HIV Antigens / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D014763:Viral Matrix Proteins / Q000502:physiology*; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D019065:Virus Assembly / Q000187:drug effects; D054301:gag Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015488:HIV Antigens; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1