Mapping of the human immunodeficiency virus type 2 envelope glycoprotein CD4 binding region and fusion domain with truncated proteins expressed by recombinant vaccinia viruses.
Human immunodeficiency virus type 2 (HIV-2) is more closely related to certain simian immunodeficiency viruses than to HIV-1. The HIV-1 and HIV-2 envelope (env) glycoproteins share only approximately 40% amino acid (aa) sequence homology. Additionally, HIV-1 and HIV-2 seem to differ in pathogenicity and in host range. In order to identify the functional domains of the HIV-2 env glycoprotein, e.g., the CD4 binding region, the membrane anchor, and the fusion site, and to compare them to equivalent sites of HIV-1, a set of recombinant vaccinia viruses (VV) was constructed expressing N-terminal overlapping env proteins of 863 (full-length gp160), 708, 534 (full-length gp120), 438, 332, 198, and 488 aa (internal deletion of aa 333-707). Upon infection, only env proteins comprising the amino-terminal half of the transmembrane protein were expressed on the cell surface. Such VV constructs also induced syncytia in CD4-positive cells. The syncytia were smaller when the cytoplasmic domain of the transmembrane protein was removed. The CD4 binding site of HIV-2 was located between the carboxy terminus of gp120 (aa 512) and aa 438. Thus the amino-terminal half of the transmembrane protein of HIV-2 is sufficient for cell surface localization of the env protein and syncytia induction. These properties are shared with the HIV-1 env protein and demonstrate a functional conservation among HIV-1 and HIV-2 despite their genetic and phenotypic heterogeneity.
Otteken
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Deutsches Primatenzentrum, Abteilung für Virologie und Immunologie, Göttingen, Germany.
Voss
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Hunsmann
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D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D000818:Animals; D002459:Cell Fusion; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D002874:Chromosome Mapping; D015870:Gene Expression; D015686:Gene Products, env / Q000096:biosynthesis* / Q000235:genetics; D015752:Genes, env / Q000235:genetics*; D015726:Giant Cells / Q000166:cytology; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis / Q000235:genetics; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000235:genetics; D015498:HIV-2 / Q000235:genetics*; D006801:Humans; D051379:Mice; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D017384:Sequence Deletion; D014616:Vaccinia virus / Q000235:genetics; D014760:Viral Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics
D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D011994:Recombinant Proteins; D014760:Viral Fusion Proteins