The HIV-1 gp120 CD4-bound conformation is preferentially targeted by antibody-dependent cellular cytotoxicity-mediating antibodies in sera from HIV-1-infected individuals. 2015

Maxime Veillette, and Mathieu Coutu, and Jonathan Richard, and Laurie-Anne Batraville, and Olina Dagher, and Nicole Bernard, and Cécile Tremblay, and Daniel E Kaufmann, and Michel Roger, and Andrés Finzi
Centre de Recherche du CHUM, Université de Montréal, Montreal, Quebec, Canada Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.

Recent studies have linked antibody Fc-mediated effector functions with protection or control of human immunodeficiency type 1 (HIV-1) and simian immunodeficiency (SIV) infections. Interestingly, the presence of antibodies with potent antibody-dependent cellular cytotoxicity (ADCC) activity in the Thai RV144 vaccine trial was suggested to correlate with decreased HIV-1 acquisition risk. These antibodies recently were found to recognize HIV envelope (Env) epitopes exposed upon Env-CD4 interaction. CD4 downregulation by Nef and Vpu, as well as Vpu-mediated BST-2 antagonism, were reported to modulate exposure of those CD4-induced HIV-1 Env epitopes and were proposed to play a role in reducing the susceptibility of infected cells to ADCC mediated by this class of antibodies. Here, we report the high prevalence of antibodies recognizing CD4-induced HIV-1 Env epitopes in sera from HIV-1-infected individuals, which correlated with their ability to mediate ADCC responses against HIV-1-infected cells, exposing these Env epitopes at the cell surface. Furthermore, our results indicate that Env variable regions V1, V2, V3, and V5 do not represent a major determinant for ADCC responses mediated by sera from HIV-1-infected individuals. Altogether, these findings suggest that HIV-1 tightly controls the exposure of certain Env epitopes at the surface of infected cells in order to prevent elimination by Fc-effector functions. OBJECTIVE Here, we identified a particular conformation of HIV-1 Env that is specifically targeted by ADCC-mediating antibodies present in sera from HIV-1-infected individuals. This observation suggests that HIV-1 developed sophisticated mechanisms to minimize the exposure of these epitopes at the surface of infected cells.

UI MeSH Term Description Entries
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000920 Antibody-Dependent Cell Cytotoxicity The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent. ADCC,Cytotoxicity, Antibody-Dependent Cell,Cell Cytoxicity, Antibody-Dependent,Antibody Dependent Cell Cytotoxicity,Antibody-Dependent Cell Cytotoxicities,Antibody-Dependent Cell Cytoxicities,Antibody-Dependent Cell Cytoxicity,Cell Cytotoxicities, Antibody-Dependent,Cell Cytotoxicity, Antibody-Dependent,Cell Cytoxicities, Antibody-Dependent,Cell Cytoxicity, Antibody Dependent,Cytotoxicities, Antibody-Dependent Cell,Cytotoxicity, Antibody Dependent Cell,Cytoxicities, Antibody-Dependent Cell,Cytoxicity, Antibody-Dependent Cell
D000939 Epitopes Sites on an antigen that interact with specific antibodies. Antigenic Determinant,Antigenic Determinants,Antigenic Specificity,Epitope,Determinant, Antigenic,Determinants, Antigenic,Specificity, Antigenic
D015331 Cohort Studies Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. Birth Cohort Studies,Birth Cohort Study,Closed Cohort Studies,Cohort Analysis,Concurrent Studies,Historical Cohort Studies,Incidence Studies,Analysis, Cohort,Cohort Studies, Closed,Cohort Studies, Historical,Studies, Closed Cohort,Studies, Concurrent,Studies, Historical Cohort,Analyses, Cohort,Closed Cohort Study,Cohort Analyses,Cohort Studies, Birth,Cohort Study,Cohort Study, Birth,Cohort Study, Closed,Cohort Study, Historical,Concurrent Study,Historical Cohort Study,Incidence Study,Studies, Birth Cohort,Studies, Cohort,Studies, Incidence,Study, Birth Cohort,Study, Closed Cohort,Study, Cohort,Study, Concurrent,Study, Historical Cohort,Study, Incidence
D015483 HIV Antibodies Antibodies reactive with HIV ANTIGENS. AIDS Antibodies,HIV-Associated Antibodies,HTLV-III Antibodies,HTLV-III-LAV Antibodies,LAV Antibodies,Lymphadenopathy-Associated Antibodies,T-Lymphotropic Virus Type III Antibodies, Human,HIV Associated Antibodies,HTLV III Antibodies,HTLV III LAV Antibodies,Lymphadenopathy Associated Antibodies,T Lymphotropic Virus Type III Antibodies, Human,Antibodies, AIDS,Antibodies, HIV,Antibodies, HIV Associated,Antibodies, HIV-Associated,Antibodies, HTLV III,Antibodies, HTLV-III,Antibodies, HTLV-III-LAV,Antibodies, LAV,Antibodies, Lymphadenopathy Associated,Antibodies, Lymphadenopathy-Associated
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D015699 HIV Envelope Protein gp120 External envelope protein of the human immunodeficiency virus which is encoded by the HIV env gene. It has a molecular weight of 120 kDa and contains numerous glycosylation sites. Gp120 binds to cells expressing CD4 cell-surface antigens, most notably T4-lymphocytes and monocytes/macrophages. Gp120 has been shown to interfere with the normal function of CD4 and is at least partly responsible for the cytopathic effect of HIV. Envelope Glycoprotein gp120, HIV,HTLV-III gp120,env Protein gp120, HIV,gp120(HIV),HIV Envelope Glycoprotein gp120,gp120 Envelope Glycoprotein, HIV,HTLV III gp120,gp120, HTLV-III
D015704 CD4 Antigens 55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. They are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. T4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120. Antigens, CD4,CD4 Molecule,CD4 Receptor,CD4 Receptors,Receptors, CD4,T4 Antigens, T-Cell,CD4 Antigen,Receptors, Surface CD4,Surface CD4 Receptor,Antigen, CD4,Antigens, T-Cell T4,CD4 Receptor, Surface,CD4 Receptors, Surface,Receptor, CD4,Surface CD4 Receptors,T-Cell T4 Antigens,T4 Antigens, T Cell

Related Publications

Maxime Veillette, and Mathieu Coutu, and Jonathan Richard, and Laurie-Anne Batraville, and Olina Dagher, and Nicole Bernard, and Cécile Tremblay, and Daniel E Kaufmann, and Michel Roger, and Andrés Finzi
January 2018, Infectious diseases (London, England),
Maxime Veillette, and Mathieu Coutu, and Jonathan Richard, and Laurie-Anne Batraville, and Olina Dagher, and Nicole Bernard, and Cécile Tremblay, and Daniel E Kaufmann, and Michel Roger, and Andrés Finzi
December 2019, mBio,
Maxime Veillette, and Mathieu Coutu, and Jonathan Richard, and Laurie-Anne Batraville, and Olina Dagher, and Nicole Bernard, and Cécile Tremblay, and Daniel E Kaufmann, and Michel Roger, and Andrés Finzi
May 2019, The Journal of infectious diseases,
Maxime Veillette, and Mathieu Coutu, and Jonathan Richard, and Laurie-Anne Batraville, and Olina Dagher, and Nicole Bernard, and Cécile Tremblay, and Daniel E Kaufmann, and Michel Roger, and Andrés Finzi
October 2015, Journal of virology,
Maxime Veillette, and Mathieu Coutu, and Jonathan Richard, and Laurie-Anne Batraville, and Olina Dagher, and Nicole Bernard, and Cécile Tremblay, and Daniel E Kaufmann, and Michel Roger, and Andrés Finzi
January 2023, Cell reports,
Maxime Veillette, and Mathieu Coutu, and Jonathan Richard, and Laurie-Anne Batraville, and Olina Dagher, and Nicole Bernard, and Cécile Tremblay, and Daniel E Kaufmann, and Michel Roger, and Andrés Finzi
November 2012, Journal of virology,
Maxime Veillette, and Mathieu Coutu, and Jonathan Richard, and Laurie-Anne Batraville, and Olina Dagher, and Nicole Bernard, and Cécile Tremblay, and Daniel E Kaufmann, and Michel Roger, and Andrés Finzi
May 2019, Journal of virology,
Maxime Veillette, and Mathieu Coutu, and Jonathan Richard, and Laurie-Anne Batraville, and Olina Dagher, and Nicole Bernard, and Cécile Tremblay, and Daniel E Kaufmann, and Michel Roger, and Andrés Finzi
December 2013, Retrovirology,
Maxime Veillette, and Mathieu Coutu, and Jonathan Richard, and Laurie-Anne Batraville, and Olina Dagher, and Nicole Bernard, and Cécile Tremblay, and Daniel E Kaufmann, and Michel Roger, and Andrés Finzi
May 2016, AIDS research and human retroviruses,
Maxime Veillette, and Mathieu Coutu, and Jonathan Richard, and Laurie-Anne Batraville, and Olina Dagher, and Nicole Bernard, and Cécile Tremblay, and Daniel E Kaufmann, and Michel Roger, and Andrés Finzi
November 1996, Clinical immunology and immunopathology,
Copied contents to your clipboard!