Coexpression of a nonsyncytium inducer HIV-1 glycoprotein inhibits syncytium formation by another HIV-1 Env protein.
The biosynthesis and biological properties of the envelope glycoprotein from a primary isolate of the human immunodeficiency virus type 1, HIV-1 YU2, and the Env product from the laboratory-adapted strain, HIV-1 LAI were compared in the absence of viral replication. We found that the level of expression and proteolytic processing into gp120/gp41 complexes of both glycoproteins was equivalent and independent of the cell type used. Although the two glycoproteins were detected on the surface of HeLa cells expressing high levels of CD4, only the HIV LAI Env product induced significant syncytium formation. Interestingly, when both glycoproteins were coexpressed in HeLa-CD4 cells, syncytium formation was greatly reduced. However, cell fusion could be restored by increasing amounts of the LAI envelope gene product. HeLa-CD4 cells expressing either glycoprotein fused with high efficiency to CEM-A cells, a hybrid of CEM and peripheral blood mononuclear cells, indicating that both glycoproteins were expressed in a biologically active form on the surface of these cells. These studies suggest that primary isolates and laboratory adapted stains may require, in addition to the CD4 receptor, independent accessory membrane components for the fusion activation step. Our results agree with the concept that virus entry requires the concerted activation of each glycoprotein subunit of the Env oligomeric complex.
Li
Y Y
YY
Molecular Biology and Biotechnology Program, Salem-Teikyo University-Tampa Bay Research Institute, St. Petersburg, Florida 33716, USA.
O'Donnell
M A
MA
Perez
L G
LG
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D015726:Giant Cells / Q000821:virology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000502:physiology*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D008562:Membrane Glycoproteins