Abstract
BackgroundEbolavirus and Marburgvirus are genera of the virus family Filoviridae. Filoviruses cause rare but fatal viral hemorrhagic fevers (VHFs) in remote villages of equatorial Africa with potential for regional and international spread. Point-of-care (POC) rapid diagnostic tests (RDTs) are critical for early epidemic detection, reponse and control. There are 2 RDTs for Zaire ebolavirus (EBOV), but not other Ebolavirus spp. or Marburg marburgvirus (MARV). We validate 3 conserved B cell epitopes of filovirus glycoprotein (GP) using ebola virus diseases (EVD) survivor samples, towards devising pan-filovirus RDTs.MethodsIn-silico Immuno-informatics:- (a) multiple and basic local alignments of amino-acid sequences of filovirus (4 Ebolavirus spp. & MARV) Gp1, 2 and epitope prediction and conservation analyses within context of ClusterW, BLAST-P and the immune epitope database analysis resource (IEDB-AR); alongside (b) in-vitro enzyme immuno-assays (EIAs) for SUDV Gp1, 2 antigen and host-specific antibodies (IgM and IgG) among 94 gamma irradiated EVD survivor serum and 9 negative controls.ResultsLinear B cell epitopes were present across the entire length of all Gp1, 2, most lying in the region between amino acids positioned 350 and 500. Three seperate epitopes 97/80_GAFFLYDRLAST, 39_YEAGEWAENCY and 500_CGLRQLANETTQALQLFLRATTELR (designated UG-Filo-Peptide− 1, 2 and 3 respectively) were conserved within all studied filovirus species Gp1, 2. Gp1, 2 host specific IgM levels were comparably low (av. ODs < 0.04 [95% CI: 0.02837 to 0.04033]) among the 9 negative controls and 57 survivor samples analyzed. Host specific IgG levels, on the other hand, were elevated (av. ODs > 1.7525 [95% CI: 0.3010 to 3.1352]) among the 92 survivor samples relative to the 9 negative controls (av. ODs < 0.2.321 [95% CI: -0.7596 to 0.5372]). Filovirus Gp1, 2 antigen was not detected [av. ODs < 0.20] within EVD survivor serum relative to recombinant protein positive controls [av. ODs = 0.50].ConclusionsThese conserved B cell epitopes of filovirus Gp1, 2 and their derivative antibodies are promising for research and development of RDTs for EVD, with potential for extension to detect MVD.
Highlights
Ebolavirus and Marburgvirus are genera of the virus family Filoviridae
Five species of the genus Ebolavirus, four of which are pathogenic to man (Sudan ebolavirusSUDV, Zaire ebolavirus (EBOV), Tai Forest ebolavirusTAFV, and Bundibugyo ebolavirus-BDBV)
The high infectiousness and case-mortality rates (23–95%) associated with either Viral hemorragic fevers (VHF) warrants the designation of both filovirus genera as class A pathogens [4, 6, 7]
Summary
Filoviruses cause rare but fatal viral hemorrhagic fevers (VHFs) in remote villages of equatorial Africa with potential for regional and international spread. Filoviruses are enveloped, non-segmented single-stranded RNA viruses of the order Mononegavirales [1] Both genera have virion particles that are pleomorphic with a long and filamentous—essentially bacillary structure [1, 2]. Two filoviruses cause rare but fatal viral hemmorhagic fever (VHFs) in remote villages of equatorial Africa, with potential for regional and international spread [1, 2]. Members of the genus Ebolavirus, on the other hand, first emerged in 1976 as the causative agent of two simultaneous VHF outbreaks in southern Sudan and northern Zaire [1, 3]. The high infectiousness and case-mortality rates (23–95%) associated with either VHFs warrants the designation of both filovirus genera as class A pathogens [4, 6, 7]
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