Identification and characterization of fusion and processing domains of the human immunodeficiency virus type 2 envelope glycoprotein.
The envelope glycoprotein of the human immunodeficiency virus type 2 (HIV-2) is synthesized as a polyprotein precursor which is proteolytically processed to produce the mature surface and transmembrane envelope glycoproteins. The processed envelope glycoprotein species are responsible for the fusion between the viral envelope and the host cell membrane during the infection process. The envelope glycoprotein also induces syncytium formation between envelope-expressing cells and receptor-bearing cells. To characterize domains of the HIV-2 envelope glycoprotein involved in membrane fusion and in proteolytic processing, we introduced single amino acid mutations into the region of the HIV-2 surface glycoprotein corresponding to the principal neutralizing determinant (the V3 loop) of HIV-1, the putative HIV-2 envelope precursor-processing sequence, and the hydrophobic amino terminus of the HIV-2 transmembrane envelope glycoprotein. The effects of these mutations on syncytium formation, virus infectivity, envelope expression, envelope processing, and CD4 binding were analyzed. Our results suggest that the V3-like region of the HIV-2 surface glycoprotein and the hydrophobic amino terminus of the transmembrane glycoprotein are HIV-2 fusion domains and characterize the effects of mutations in the HIV-2 envelope glycoprotein precursor-processing sequence.
Freed
E O
EO
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.
Myers
D J
DJ
D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000378:metabolism; D002459:Cell Fusion; D004252:DNA Mutational Analysis; D015686:Gene Products, env / Q000235:genetics* / Q000378:metabolism; D015726:Giant Cells; D015488:HIV Antigens / Q000235:genetics / Q000378:metabolism; D015498:HIV-2 / Q000235:genetics* / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011499:Protein Processing, Post-Translational; D014760:Viral Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence
D015704:CD4 Antigens; D015686:Gene Products, env; D015488:HIV Antigens; D014760:Viral Fusion Proteins