title: HIV-1 ENVELOPE. Effect of the cytoplasmic domain on antigenic characteristics of HIV-1 envelope glycoprotein.
abstract: A major goal for HIV-1 vaccine development is the production of an immunogen to mimic native, functional HIV-1 envelope trimeric spikes (Env) on the virion surface. We lack a reliable description of a native, functional trimer, however, because of inherent instability and heterogeneity in most preparations. We describe here two conformationally homogeneous Envs derived from difficult-to-neutralize primary isolates. All their non-neutralizing epitopes are fully concealed and independent of their proteolytic processing. Most broadly neutralizing antibodies (bnAbs) recognize these native trimers. Truncation of their cytoplasmic tail has little effect on membrane fusion, but it diminishes binding to trimer-specific bnAbs while exposing non-neutralizing epitopes. These results yield a more accurate antigenic picture than hitherto possible of a genuinely untriggered and functional HIV-1 Env; they can guide effective vaccine development.
authors.affiliation: Division of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA. Department of Pediatrics, Harvard Medical School, 3 Blackfan Street, Boston, MA 02115, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA. Department of Pediatrics, Harvard Medical School, 3 Blackfan Street, Boston, MA 02115, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Kovacs
authors.affiliation: Division of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Hanqin
authors.initials: H
authors.lastname: Peng
authors.affiliation: Division of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Rits-Volloch
authors.affiliation: Codex BioSolutions, Inc., 401 Professional Drive, Gaithersburg, MD 20879, USA.
authors.forename: Jianming
authors.initials: J
authors.lastname: Lu
authors.affiliation: Division of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Donghyun
authors.initials: D
authors.lastname: Park
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Elise
authors.initials: E
authors.lastname: Zablowsky
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: Division of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA. Department of Pediatrics, Harvard Medical School, 3 Blackfan Street, Boston, MA 02115, USA. bchen@crystal.harvard.edu.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D000941:Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D003593:Cytoplasm / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000737:chemistry / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D017434:Protein Structure, Tertiary; D014771:Virion / Q000737:chemistry / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000941:Antigens; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; C514793:gp120 protein, Human immunodeficiency virus 1; C514797:gp160 protein, Human immunodeficiency virus 1; C514787:gp41 protein, Human immunodeficiency virus 1