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Structure of Simian Immunodeficiency Virus Envelope Spikes Bound with CD4 and Monoclonal Antibody 36D5.

Title: Structure of Simian Immunodeficiency Virus Envelope Spikes Bound with CD4 and Monoclonal Antibody 36D5.
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Name(s): Hu, Guiqing, author
Liu, Jun, author
Roux, Kenneth H, author
Taylor, Kenneth A, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2017-07-27
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus (SIV) envelope spike (Env) mediates viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the coreceptor binding site and is a target for neutralizing antibodies. We used cryo-electron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody (MAb) 36D5 to gp120 of the SIV Env trimer. Our results show that 36D5 binds gp120 at the base of the V3 loop and suggest that the antibody exerts its neutralization effect by blocking the coreceptor binding site. The antibody does this without altering the dynamics of the spike motion between closed and open states when CD4 is bound. The interaction between 36D5 and SIV gp120 is similar to the interaction between some broadly neutralizing anti-V3 loop antibodies and HIV-1 gp120. Two conformations of gp120 bound with CD4 are revealed, suggesting an intrinsic dynamic nature of the liganded Env trimer. CD4 binding substantially increases the binding of 36D5 to gp120 in the intact Env trimer, consistent with CD4-induced changes in the conformation of gp120 and the antibody binding site. Binding by MAb 36D5 does not substantially alter the proportions of the two CD4-bound conformations. The position of MAb 36D5 at the V3 base changes little between conformations, indicating that the V3 base serves as a pivot point during the transition between these two states. Glycoprotein spikes on the surfaces of SIV and HIV are the sole targets available to the immune system for antibody neutralization. Spikes evade the immune system by a combination of a thick layer of polysaccharide on the surface (the glycan shield) and movement between spike domains that masks the epitope conformation. Using SIV virions whose spikes were "decorated" with the primary cellular receptor (CD4) and an antibody (36D5) at part of the coreceptor binding site, we visualized multiple conformations trapped by the rapid freezing step, which were separated using statistical analysis. Our results show that the CD4-induced conformational dynamics of the spike enhances binding of the antibody.
Identifier: FSU_pmch_28539445 (IID), 10.1128/JVI.00134-17 (DOI), PMC5533903 (PMCID), 28539445 (RID), 28539445 (EID), JVI.00134-17 (PII)
Keywords: AIDS, HIV, Cryo-electron tomography, Electron microscopy, Image processing, Immunology
Grant Number: R01 AI055461
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533903.
Subject(s): Antibodies, Monoclonal/chemistry
Antibodies, Monoclonal/metabolism
Antibodies, Neutralizing/chemistry
Antibodies, Neutralizing/metabolism
Antibodies, Viral/chemistry
Antibodies, Viral/metabolism
CD4 Antigens/chemistry
CD4 Antigens/metabolism
Electron Microscope Tomography
Membrane Glycoproteins/chemistry
Membrane Glycoproteins/metabolism
Models, Molecular
Protein Binding
Protein Conformation
Protein Multimerization
Viral Envelope Proteins/chemistry
Viral Envelope Proteins/metabolism
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_28539445
Owner Institution: FSU
Is Part Of: Journal of virology.
1098-5514
Issue: iss. 16, vol. 91

Choose the citation style.
Hu, G., Liu, J., Roux, K. H., & Taylor, K. A. (2017). Structure of Simian Immunodeficiency Virus Envelope Spikes Bound with CD4 and Monoclonal Antibody 36D5. Journal Of Virology. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_28539445