title: Identifying possible sites for antibody neutralization escape: Implications for unique functional properties of the C-terminal tail of Human Immunodeficiency Virus Type 1 gp41.
abstract: A previous amino acid sequence analyses from our laboratory reported nine potential sites in gp41 glycoprotein of HIV-1 that may contribute to virus escape from antibody neutralization. Besides four sites found outside the membrane of HIV-1 virus, five located in the C-terminal tail of gp41 specifically in the lentivirus lytic peptides motifs (LLPs). To further study the bioinformatical results, the virus infectivity assay and the standard neutralization assay were conducted on conservatively mutated virus. Two sites in the LLP3 domain stood out with the ability to alter the resistance of HIV-1 virus to certain broadly neutralizing antibodies (bNAbs). While the glycoprotein incorporation on the viral membrane and the interaction of the LLP3 domain with the lipid membrane remained unaltered, the increase in neutralization resistance of the mutant virus was associated with the changes on Env conformation. Our findings demonstrate different sensibility of bNAbs to mutations in the C-terminal tail and indicate an unrecognized potential role for even minor sequence variation in the C-terminal tail in modulating the antigenicity of the ectodomain of HIV-1 envelope glycoprotein complex.
authors.affiliation: Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, MOE Key Laboratory for Protein Sciences, Beijing 100084, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, MOE Key Laboratory for Protein Sciences, Beijing 100084, China.
authors.forename: Yushen
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, MOE Key Laboratory for Protein Sciences, Beijing 100084, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, MOE Key Laboratory for Protein Sciences, Beijing 100084, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, MOE Key Laboratory for Protein Sciences, Beijing 100084, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing Key Laboratory for Protein Therapeutics, MOE Key Laboratory for Protein Sciences, Beijing 100084, China. Electronic address: chenyh@mail.tsinghua.edu.cn.
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Chen
mesh_terms: D057134:Antibodies, Neutralizing / Q000378:metabolism; D000940:Antigenic Variation / Q000235:genetics; D019295:Computational Biology; D018985:Epitopes, B-Lymphocyte / Q000235:genetics; D005818:Genetic Engineering; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D056724:Immunity, Humoral; D009154:Mutation / Q000235:genetics; D011487:Protein Conformation; D000072417:Protein Domains / Q000235:genetics
chemical_list: D057134:Antibodies, Neutralizing; D018985:Epitopes, B-Lymphocyte; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1
keywords: C-terminal tail; HIV-1; Immune escape