Glycoprotein of human immunodeficiency virus type 1 synthesized in chronically infected Molt3 cells acquires heterogeneous oligosaccharide structures.
Diversity of oligosaccharide structures on the glycoprotein of HIV-1 was studied in individual clones of Molt3 cells chronically infected with HIV-1IIIB. A glycoprotein of molecular weight 140 kD (gp140) was found to be shed into the medium from one of these clones, which unlike normally processed gp120, contained significant proportions of endo H resistant oligosaccharides. Treatment of infected cells with the inhibitors of oligosaccharide trimming enzymes affected the glycosylation pattern as well as the secretion of the glycoprotein into the medium. The exposure of the principal neutralizing domain (PND) on the surface of gp140, as measured by its accessibility to thrombin cleavage, was comparable to that observed with gp120. Sera obtained from mice inoculated with purified gp140 contained high titered anti-V3 antibodies and blocked HIV-1IIIB-induced syncytium formation. These results demonstrate that although glycosylation of viral glycoproteins is governed by the host cell glycosyl transferases, glycoprotein secreted from biological clones of the same host cells acquires different oligosaccharide structures. Exposure and immunogenicity of the PND in one such glycosylation variant are comparable to the normally processed gp120 molecule.
Pal
R
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Advanced BioScience Laboratories, Inc., Kensington, Maryland 20895.
di Marzo Veronese
F
F
Nair
B C
BC
Rittenhouse
S
S
Hoke
G
G
Mumbauer
S
S
Sarngadharan
M G
MG
D002474:Cell-Free System; D002999:Clone Cells; D015726:Giant Cells; D006023:Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D006031:Glycosylation; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008715:Methionine / Q000378:metabolism; D009844:Oligosaccharides / Q000032:analysis / Q000096:biosynthesis*; D010446:Peptide Fragments / Q000302:isolation & purification; D011487:Protein Conformation; D013462:Sulfur Radioisotopes; D013917:Thrombin; D014759:Viral Envelope Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification
D006023:Glycoproteins; D009844:Oligosaccharides; D010446:Peptide Fragments; D013462:Sulfur Radioisotopes; D014759:Viral Envelope Proteins; D008715:Methionine; D013917:Thrombin