Human immunodeficiency virus type 2 envelope glycoprotein: differential CD4 interactions of soluble gp120 versus the assembled envelope complex.
Utilizing a recombinant vaccinia expression system, we investigated the biological properties and CD4 receptor interactions of the envelope glycoproteins of a noncytopathic human immunodeficiency virus type 2 strain, termed HIV-2/ST, and a highly cytopathic variant derived from it. The efficiency and host cell range of syncytium formation by the recombinant glycoproteins of both viruses were highly restricted compared to those of prototypic strains of HIV (HIV-2/ROD or HIV-1/IIIB). However, the glycoprotein of cytopathic but not wild-type ST generated numerous large syncytia in the human T-cell line Sup T1 from which it was derived. A single cell line (Molt 4 clone 8) was permissive to fusion by both wild-type and cytopathic ST envelopes, but only the glycoprotein of cytopathic ST could be inhibited with a soluble form of the viral receptor CD4 (sCD4). While these results indicated major differences in the envelope glycoprotein-CD4 receptor interactions of wild-type versus cytopathic ST, direct and competition binding assays utilizing soluble external glycoprotein (SU) and sCD4 surprisingly revealed equivalent low binding affinity for both viruses. From these experiments we conclude that relevant biological properties (e.g., CD4 binding, cytopathic potential, and sCD4 neutralization) of HIV viruses which differ in their pathogenic potential are reflected in the sCD4 interactions of the assembled native envelope complex (as on cell or virion surfaces) but not the soluble SU glycoprotein.
Mulligan
M J
MJ
Department of Medicine, University of Alabama, Birmingham 35294.
Ritter
G D
GD
Chaikin
M A
MA
Yamshchikov
G V
GV
Kumar
P
P
Hahn
B H
BH
Sweet
R W
RW
Compans
R W
RW
D015704:CD4 Antigens / Q000378:metabolism*; D002459:Cell Fusion / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D015726:Giant Cells; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015498:HIV-2 / Q000378:metabolism*; D015151:Immunoblotting; D007700:Kinetics; D046911:Macromolecular Substances; D011869:Radioligand Assay; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility; D014616:Vaccinia virus / Q000235:genetics
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D046911:Macromolecular Substances; D011994:Recombinant Proteins