Virion incorporation of envelope glycoproteins with long but not short cytoplasmic tails is blocked by specific, single amino acid substitutions in the human immunodeficiency virus type 1 matrix.
Incorporation of envelope glycoproteins into a budding retrovirus is an essential step in the formation of an infectious virus particle. By using site-directed mutagenesis, we identified specific amino acid residues in the matrix domain of the human immunodeficiency virus type 1 (HIV-1) Gag protein that are critical to the incorporation of HIV-1 envelope glycoproteins into virus particles. Pseudotyping analyses were used to demonstrate that two heterologous envelope glycoproteins with short cytoplasmic tails (the envelope of the amphotropic murine leukemia virus and a naturally truncated HIV-2 envelope) are efficiently incorporated into HIV-1 particles bearing the matrix mutations. Furthermore, deletion of the cytoplasmic tail of HIV-1 transmembrane envelope glycoprotein gp41 from 150 to 7 or 47 residues reversed the incorporation block imposed by the matrix mutations. These results suggest the existence of a specific functional interaction between the HIV-1 matrix and the gp41 cytoplasmic tail.
Freed
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Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0460.
Martin
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D003593:Cytoplasm; D015683:Gene Products, gag / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000378:metabolism; D015497:HIV-1 / Q000648:ultrastructure*; D015498:HIV-2 / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D009052:Leukemia Virus, Murine / Q000648:ultrastructure; D009024:Morphogenesis; D016297:Mutagenesis, Site-Directed; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism; D014779:Virus Replication
D015683:Gene Products, gag; D015700:HIV Envelope Protein gp41; D014759:Viral Envelope Proteins