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Structural basis for the antibody neutralization of herpes simplex virus.

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Lee CC, Lin LL, Chan WE, Ko TP, Lai JS, Wang AH
OpenAccess logo Acta Crystallogr D Biol Crystallogr 69 1935-45 (2013)
Cited: 33 times
EuropePMC logo PMID: 24100313

Abstract

Glycoprotein D (gD) of herpes simplex virus (HSV) binds to a host cell surface receptor, which is required to trigger membrane fusion for virion entry into the host cell. gD has become a validated anti-HSV target for therapeutic antibody development. The highly inhibitory human monoclonal antibody E317 (mAb E317) was previously raised against HSV gD for viral neutralization. To understand the structural basis of antibody neutralization, crystals of the gD ectodomain bound to the E317 Fab domain were obtained. The structure of the complex reveals that E317 interacts with gD mainly through the heavy chain, which covers a large area for epitope recognition on gD, with a flexible N-terminal and C-terminal conformation. The epitope core structure maps to the external surface of gD, corresponding to the binding sites of two receptors, herpesvirus entry mediator (HVEM) and nectin-1, which mediate HSV infection. E317 directly recognizes the gD-nectin-1 interface and occludes the HVEM contact site of gD to block its binding to either receptor. The binding of E317 to gD also prohibits the formation of the N-terminal hairpin of gD for HVEM recognition. The major E317-binding site on gD overlaps with either the nectin-1-binding residues or the neutralizing antigenic sites identified thus far (Tyr38, Asp215, Arg222 and Phe223). The epitopes of gD for E317 binding are highly conserved between two types of human herpesvirus (HSV-1 and HSV-2). This study enables the virus-neutralizing epitopes to be correlated with the receptor-binding regions. The results further strengthen the previously demonstrated therapeutic and diagnostic potential of the E317 antibody.

Articles - 3w9d mentioned but not cited (6)

  1. Structural basis for the antibody neutralization of herpes simplex virus. Lee CC, Lin LL, Chan WE, Ko TP, Lai JS, Wang AH. Acta Crystallogr D Biol Crystallogr 69 1935-1945 (2013)
  2. Improving Loop Modeling of the Antibody Complementarity-Determining Region 3 Using Knowledge-Based Restraints. Finn JA, Koehler Leman J, Willis JR, Cisneros A, Crowe JE, Meiler J. PLoS One 11 e0154811 (2016)
  3. Structural basis of polyethylene glycol recognition by antibody. Lee CC, Su YC, Ko TP, Lin LL, Yang CY, Chang SS, Roffler SR, Wang AH. J Biomed Sci 27 12 (2020)
  4. High throughput discovery of influenza virus neutralizing antibodies from phage-displayed synthetic antibody libraries. Chen IC, Chiu YK, Yu CM, Lee CC, Tung CP, Tsou YL, Huang YJ, Lin CL, Chen HS, Wang AH, Yang AS. Sci Rep 7 14455 (2017)
  5. Canonical structures of short CDR-L3 in antibodies. Teplyakov A, Gilliland GL. Proteins 82 1668-1673 (2014)
  6. Characterizing Epitope Binding Regions of Entire Antibody Panels by Combining Experimental and Computational Analysis of Antibody: Antigen Binding Competition. Brooks BD, Closmore A, Yang J, Holland M, Cairns T, Cohen GH, Bailey-Kellogg C. Molecules 25 E3659 (2020)


Reviews citing this publication (7)

  1. The structural basis of herpesvirus entry. Connolly SA, Jardetzky TS, Longnecker R. Nat Rev Microbiol 19 110-121 (2021)
  2. Bacteriophages and Their Immunological Applications against Infectious Threats. Criscuolo E, Spadini S, Lamanna J, Ferro M, Burioni R. J Immunol Res 2017 3780697 (2017)
  3. Protein- and Peptide-Based Virus Inactivators: Inactivating Viruses Before Their Entry Into Cells. Su X, Wang Q, Wen Y, Jiang S, Lu L. Front Microbiol 11 1063 (2020)
  4. Oncolytic virotherapy evolved into the fourth generation as tumor immunotherapy. Wang X, Shen Y, Wan X, Hu X, Cai WQ, Wu Z, Xin Q, Liu X, Gui J, Xin HY, Xin HW. J Transl Med 21 500 (2023)
  5. Role and potential therapeutic use of antibodies against herpetic infections. Clementi N, Cappelletti F, Criscuolo E, Castelli M, Mancini N, Burioni R, Clementi M. Clin Microbiol Infect 23 381-386 (2017)
  6. Monoclonal antibody therapy of herpes simplex virus: An opportunity to decrease congenital and perinatal infections. Backes IM, Leib DA, Ackerman ME. Front Immunol 13 959603 (2022)
  7. A critical review on antiviral peptides derived from viral glycoproteins and host receptors to decoy herpes simplex virus. Rahangdale R, Tender T, Balireddy S, Goswami K, Pasupuleti M, Hariharapura RC. Microb Biotechnol 16 2036-2052 (2023)

Articles citing this publication (20)



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