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PLoS Pathog. 2014 Dec 4;10(12):e1004495. doi: 10.1371/journal.ppat.1004495. eCollection 2014 Dec.

Murine anti-vaccinia virus D8 antibodies target different epitopes and differ in their ability to block D8 binding to CS-E.

Author information

1
Division of Cell Biology, La Jolla Institute for Allergy and Imunology (LIAI), La Jolla, California, United States of America.
2
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
3
Howard Hughes Medical Institute, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, United States of America.
4
Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, Texas, United States of America.
5
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology (LIAI), La Jolla, California, United States of America.

Abstract

The IMV envelope protein D8 is an adhesion molecule and a major immunodominant antigen of vaccinia virus (VACV). Here we identified the optimal D8 ligand to be chondroitin sulfate E (CS-E). CS-E is characterized by a disaccharide moiety with two sulfated hydroxyl groups at positions 4' and 6' of GalNAc. To study the role of antibodies in preventing D8 adhesion to CS-E, we have used a panel of murine monoclonal antibodies, and tested their ability to compete with CS-E for D8 binding. Among four antibody specificity groups, MAbs of one group (group IV) fully abrogated CS-E binding, while MAbs of a second group (group III) displayed widely varying levels of CS-E blocking. Using EM, we identified the binding site for each antibody specificity group on D8. Recombinant D8 forms a hexameric arrangement, mediated by self-association of a small C-terminal domain of D8. We propose a model in which D8 oligomerization on the IMV would allow VACV to adhere to heterogeneous population of CS, including CS-C and potentially CS-A, while overall increasing binding efficiency to CS-E.

PMID:
25474621
PMCID:
PMC4256255
DOI:
10.1371/journal.ppat.1004495
[Indexed for MEDLINE]
Free PMC Article

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