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

• Main Authors: Michael H Matho, Natalia de Val, Gregory M Miller, Joshua Brown, Andrew Schlossman, Xiangzhi Meng, Shane Crotty, Bjoern Peters, Yan Xiang, Linda C Hsieh-Wilson, Andrew B Ward, Dirk M Zajonc
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2014-12-01
• Series: PLoS Pathogens
• Online Access: http://europepmc.org/articles/PMC4256255?pdf=render

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.