title: Sensitivity of transmitted and founder human immunodeficiency virus type 1 envelopes to carbohydrate-binding agents griffithsin, cyanovirin-N and Galanthus nivalis agglutinin.
abstract: Human immunodeficiency virus type 1 (HIV-1) transmission often results from infection by a single transmitted/founder (T/F) virus. Here, we investigated the sensitivity of T/F HIV-1 envelope glycoproteins (Envs) to microbicide candidate carbohydrate-binding agents (CBAs) griffithsin (GRFT), cyanovirin-N (CV-N) and Galanthus nivalis agglutinin (GNA), showing that T/F Envs demonstrated different sensitivity to CBAs, with IC50 values ranging from 0.006 ± 0.0003 to >10 nM for GRFT, from 0.6 ± 0.2 to 28.9 ± 2.9 nM for CV-N and from 1.3 ± 0.2 to >500 nM for GNA. We further revealed that deglycosylation at position 295 or 448 decreased the sensitivity of T/F Env to GRFT, and at 339 to both CV-N and GNA. Mutation of all the three glcyans rendered a CBA-sensitive T/F Env largely resistant to GRFT, indicating that the sensitivity of T/F Env to GRFT is mainly determined by glycans at 295, 339 and 448. Our study identified specific T/F Env residues associated with CBA sensitivity.
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.|University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Bodan
authors.initials: B
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Du
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.|University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.|University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Sukun
authors.initials: S
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Institute 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: D000373:Agglutinins / Q000737:chemistry / Q000494:pharmacology*; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology*; D002352:Carrier Proteins / Q000494:pharmacology*; D027801:Galanthus / Q000737:chemistry*; D015967:Gene Expression Regulation, Viral; D015699:HIV Envelope Protein gp120; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D037121:Plant Lectins / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000373:Agglutinins; D019380:Anti-HIV Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D015699:HIV Envelope Protein gp120; D037121:Plant Lectins; D014759:Viral Envelope Proteins; C107733:cyanovirin N; C499654:griffithsin protein, Griffithsia