title: Removal of two high-mannose N-linked glycans on gp120 renders human immunodeficiency virus 1 largely resistant to the carbohydrate-binding agent griffithsin.
abstract: High-mannose N-linked glycans recognized by carbohydrate-binding agents (CBAs) are potential targets for topical microbicides. To better understand the mechanisms by which CBAs inhibit human immunodeficiency virus (HIV)-1 infection at the molecular level, we systematically analysed the contribution of site-specific glycans to the anti-HIV activity of CBAs by site-directed mutagenesis. Our results demonstrate that a single deglycosylation at N295 or N448 in a range of primary and T-cell-line-adapted HIV-1 isolates resulted in marked resistance to griffithsin (GRFT) but maintained the sensitivity to cyanovirin (CV-N), Galanthus nivalis agglutinin (GNA) and a range of neutralizing antibodies. Unlike CV-N and GNA, the interaction between GRFT and gp120 appeared to be dependent on the specific trimeric 'sugar tower' including N295 and N448. This was further strengthened by the results of GRFT-Env binding experiments. Our study identifies GRFT-specific gp120 glycans and may provide information for the design of novel CBA antiviral strategies.
authors.affiliation: Graduate School, Chinese Academy of Sciences, Beijing 100049, PR China.|State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Graduate School, Chinese Academy of Sciences, Beijing 100049, PR China.|State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.affiliation: Center for Infection and Immunity, St George's University of London, London SW17 0RE, UK.
authors.forename: George E
authors.initials: GE
authors.lastname: Griffin
authors.affiliation: Center for Infection and Immunity, St George's University of London, London SW17 0RE, UK.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
authors.affiliation: Center for Infection and Immunity, St George's University of London, London SW17 0RE, UK.|State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Qinxue
authors.initials: Q
authors.lastname: Hu
mesh_terms: D020418:Algal Proteins / Q000378:metabolism*; D057134:Antibodies, Neutralizing / Q000378:metabolism; D000998:Antiviral Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D006031:Glycosylation; D015483:HIV Antibodies / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism*; D037241:Mannose-Binding Lectins / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D037121:Plant Lectins / Q000378:metabolism; D011485:Protein Binding
chemical_list: D020418:Algal Proteins; D057134:Antibodies, Neutralizing; D000998:Antiviral Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D037102:Lectins; D037241:Mannose-Binding Lectins; D037121:Plant Lectins; C514793:gp120 protein, Human immunodeficiency virus 1; C063117:snowdrop lectin; C107733:cyanovirin N; D008358:Mannose; C499654:griffithsin protein, Griffithsia