title: Highly conserved HIV-1 gp120 glycans proximal to CD4-binding region affect viral infectivity and neutralizing antibody induction.
abstract: Glycosylation plays important roles in gp120 structure and HIV-1 immune evasion. In the current study, we introduced deglycosylations into the 24 N-linked glycosylation sites of a R5 env MWS2 cloned from semen and systematically analyzed the impact on infectivity, antigenicity, immunogenicity and sensitivity to entry inhibitors. We found that mutants N156-T158A, N197-S199A, N262-S264A and N410-T412A conferred decreased infectivity and enhanced sensitivity to a series of antibodies and entry inhibitors. When mice were immunized with the DNA of wild-type or mutated gp160, gp140 or gp120; N156-T158A, N262-S264A and N410-T412A were more effective in inducing neutralizing activity against wild-type MWS2 as well as heterologous IIIB and CH811 Envs. In general, gp160 and gp140 induced higher neutralizing activity compared with gp120. Our study demonstrates for the first time that removal of individual glycan N156, N262 or N410 proximal to CD4-binding region impairs viral infectivity and results in enhanced capability to induce neutralizing activity.
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; Graduate School, Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Sukun
authors.initials: S
authors.lastname: Luo
authors.forename: Tao
authors.initials: T
authors.lastname: Du
authors.forename: George E
authors.initials: GE
authors.lastname: Griffin
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
authors.forename: Qinxue
authors.initials: Q
authors.lastname: Hu
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D017124:Conserved Sequence; D005260:Female; D006031:Glycosylation; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000276:immunology*; D011485:Protein Binding
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011134:Polysaccharides