The Lyssavirus glycoprotein: A key to cross-immunity

Virology. 2016 Nov:498:250-256. doi: 10.1016/j.virol.2016.08.034. Epub 2016 Sep 9.

Abstract

Rabies is an acute viral encephalomyelitis in warm-blooded vertebrates, caused by viruses belonging to Rhabdovirus family and genus Lyssavirus. Although rabies is categorised as a neglected disease, the rabies virus (RABV) is the most studied amongst Lyssaviruses which show nearly identical infection patterns. In efforts to improving post-exposure prophylaxis, several anti-rabies monoclonal antibodies (mAbs) targeting the glycoprotein (G protein) sites I, II, III and G5 have been characterized. To explore cross-neutralization capacity of available mAbs and discover new possible B-cell epitopes, we have analyzed all available glycoprotein sequences from Lyssaviruses with a focus on sequence variation and conservation. This information was mapped on the structure of a representative G protein. We proposed several possible cross-neutralizing B-cell epitopes (GUVTTTF, WLRTV, REECLD and EHLVVEEL) in complement to the already well-characterized antigenic sites. The research could facilitate development of novel cross-reactive mAbs against RABV and even more broad, against possibly all Lyssavirus members.

Keywords: Cross-neutralization; Glycoprotein; Lyssavirus; Rabies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antigens, Viral / chemistry
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Conserved Sequence
  • Cross Reactions / immunology*
  • Epitopes, B-Lymphocyte / chemistry
  • Epitopes, B-Lymphocyte / genetics
  • Epitopes, B-Lymphocyte / immunology
  • Glycoproteins / chemistry
  • Glycoproteins / genetics
  • Glycoproteins / immunology*
  • Lyssavirus / classification
  • Lyssavirus / genetics
  • Lyssavirus / immunology*
  • Lyssavirus / metabolism*
  • Models, Molecular
  • Neutralization Tests
  • Phylogeny
  • Protein Conformation
  • Rhabdoviridae Infections / immunology*
  • Rhabdoviridae Infections / virology*
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Epitopes, B-Lymphocyte
  • Glycoproteins
  • Viral Proteins