N-Glycans in the gp120 V1/V2 domain of the HIV-1 strain NL4-3 are indispensable for viral infectivity and resistance against antibody neutralization.
Here we report that N-glycans within the V1/V2 variable regions of the NL4-3 gp120 glycoprotein are indispensable to maintain viral functionality and are masking neutralizing epitopes. Fifteen variants of HIV-1 isolate NL4-3 with mutations of the six N-glycosylation sites g2-g7 within the V1 (g2-g4) and V2 loop (g5-g7) of gp120 were analyzed for viral infectivity and their sensitivity to neutralization. Presence of the N-glycans g4, g5, g6 and g7 was an important prerequisite to maintain viral infectivity, since virus mutants lacking these N-glycans were highly deficient in virus entry. Lack of g4 or g7 correlated to a reduction of infectivity to less than 3% of the infectivity observed for NL4-3 wild type. In contrast, mutants lacking N-glycans g2 and g3 showed a 50% increase in infectivity compared to NL4-3. Mutants lacking g2, g3, g5 and g6 with an infectivity of more than 10% of the NL4-3 wt virus were tested for neutralization and showed a high sensitivity against human serum antibody from HIV-1 infected individuals.
Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359 Hamburg, Germany.
Tobias
T
Wolk
Michael
M
Schreiber
D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D009500:Neutralization Tests; D011134:Polysaccharides / Q000502:physiology*
D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011134:Polysaccharides