The Lyssavirus glycoprotein: A key to cross-immunity.
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.
Council for Scientific and Industrial Research, Biosciences Unit, Pretoria, South Africa; Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.
Sindisiwe G
SG
Buthelezi
Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.
Heini W
HW
Dirr
Council for Scientific and Industrial Research, Biosciences Unit, Pretoria, South Africa.
Ereck
E
Chakauya
Council for Scientific and Industrial Research, Biosciences Unit, Pretoria, South Africa.
Rachel
R
Chikwamba
Unit for Computational Omics and Systems Biology, Medical Biotechnology Center, VIB, Ghent, Belgium; Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Lennart
L
Martens
Council for Scientific and Industrial Research, Biosciences Unit, Pretoria, South Africa.
Tsepo L
TL
Tsekoa
Council for Scientific and Industrial Research, Biosciences Unit, Pretoria, South Africa. Electronic address: Sstoychev@csir.co.za.
Stoyan H
SH
Stoychev
Unit for Computational Omics and Systems Biology, Medical Biotechnology Center, VIB, Ghent, Belgium; Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; Bioinformatics Institute Gent, Ghent University, Ghent, Belgium.
Elien
E
Vandermarliere
D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D017124:Conserved Sequence; D003429:Cross Reactions / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D018114:Lyssavirus / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008958:Models, Molecular; D009500:Neutralization Tests; D010802:Phylogeny; D011487:Protein Conformation; D018353:Rhabdoviridae Infections / Q000276:immunology* / Q000821:virology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D018985:Epitopes, B-Lymphocyte; D006023:Glycoproteins; D014764:Viral Proteins
Cross-neutralization; Glycoprotein; Lyssavirus; Rabies