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Ligand accessibility to the HIV-1 Env co-receptor binding site can occur prior to CD4 engagement and is independent of viral tier category

  1. Author:
    Boliar, Saikat
    Patil, Shilpa
    Shukla, Brihaspati N
    Ghobbeh, Ali
    Deshpande, Suprit
    Chen, Weizao
    Guenaga, Javier
    Dimitrov, Dimiter S
    Wyatt, Richard T
    Chakrabarti, Bimal K

  2. Author Address

    THSTI-IAVI HIV Vaccine Translational Research Laboratory, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana 121001, India., IAVI Neutralizing Antibody Center at TSRI, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA., Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., IAVI Neutralizing Antibody Center at TSRI, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: wyatt@scripps.edu., THSTI-IAVI HIV Vaccine Translational Research Laboratory, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana 121001, India; IAVI Neutralizing Antibody Center at TSRI, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: bimal.chakrabarti@ablinc.com.,
    1. Year: 2018
    2. Date: Jun
    3. Epub Date: 2018 04 20
  2. Journal: Virology
    1. 519
    2. Pages: 99-105
  4. Type of Article: Article
  5. ISSN: 0042-6822
  1. Abstract:

    HIV-1 virus entry into target cells requires the envelope glycoprotein (Env) to first bind the primary receptor, CD4 and subsequently the co-receptor. Antibody access to the co-receptor binding site (CoRbs) in the pre-receptor-engaged state, prior to cell attachment, remains poorly understood. Here, we have demonstrated that for tier-1 Envs, the CoRbs is directly accessible to full-length CD4-induced (CD4i) antibodies even before primary receptor engagement, indicating that on these Envs the CoRbs site is either preformed or can conformationally sample post-CD4-bound state. Tier-2 and tier-3 Envs, which are resistant to full-length CD4i antibody, are neutralized by m36.4, a lower molecular mass of CD4i-directed domain antibody. In some tier-2 and tier-3 Envs, CoRbs is accessible to m36.4 even prior to cellular attachment in an Env-specific manner independent of their tier category. These data suggest differential structural arrangements of CoRbs and varied masking of ligand access to the CoRbs in different Env isolates. Copyright © 2018 Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.virol.2018.04.002
  3. PMID: 29684630
  4. View record in Web of Science®
  5. WOS: 000435228000012
  6. PII : S0042-6822(18)30110-7

Library Notes

  1. Fiscal Year: FY2017-2018
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