Nonrandom distribution of gp120 N-linked glycosylation sites important for infectivity of human immunodeficiency virus type 1.
More than 20 consensus N-linked glycosylation sites occur in the gp120 coding sequence of most isolates of human immunodeficiency virus type 1. Based on the N-linked glycosylation pattern of a well-characterized recombinant gp120, it is likely that N-linked sugars are present at most, if not all, of the consensus glycosylation sites of the heavily glycosylated gp120. In this study, we evaluated the relative importance of each of the 24 N-linked glycosylation sites of gp120 in the molecular clone HXB2 to viral infectivity. The ability of HXB2-derived mutants, each having 1 of the 24 N-linked glycosylation sites mutated by site-directed mutagenesis, to infect CD4-positive SupT1 cells was compared with that of the wild-type virus. We found that most of the individual consensus N-linked glycosylation sites are dispensable for viral infectivity. The five consensus N-linked glycosylation sites that are likely to have important roles in infectivity are all located in the amino-terminal half of gp120, indicating that the N-linked glycosylation sites that are important for infectivity of human immunodeficiency virus type 1 are not randomly distributed in gp120. We predict that a partially glycosylated gp120 with most of the dispensable N-linked glycosylation sites removed may be a better vaccine candidate than the fully glycosylated gp120.
Lee
W R
WR
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115.
Syu
W J
WJ
Du
B
B
Matsuda
M
M
Tan
S
S
Wolf
A
A
Essex
M
M
Lee
T H
TH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000502:physiology; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D015752:Genes, env; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D011533:Proviruses / Q000235:genetics / Q000472:pathogenicity; D014162:Transfection
D015704:CD4 Antigens; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; D009838:Oligodeoxyribonucleotides