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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / chemistry*
  • Antibodies, Viral / immunology
  • Chondroitin Sulfates / chemistry*
  • Chondroitin Sulfates / immunology
  • Epitopes / chemistry*
  • Epitopes / immunology
  • Mice
  • Vaccinia virus / chemistry*
  • Vaccinia virus / immunology
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Viral Envelope Proteins
  • Chondroitin Sulfates