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Identity and validity of conserved B cell epitopes of filovirus glycoprotein: towards rapid diagnostic testing for Ebola and possibly Marburg virus disease

BACKGROUND: Ebolavirus 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 cri...

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Autores principales: Babirye, Peace, Musubika, Carol, Kirimunda, Samuel, Downing, Robert, Lutwama, Julian J, Mbidde, Edward K, Weyer, Jacqueline, Paweska, Janusz T, Joloba, Moses L, Wayengera, Misaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171133/
https://www.ncbi.nlm.nih.gov/pubmed/30285648
http://dx.doi.org/10.1186/s12879-018-3409-x
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author Babirye, Peace
Musubika, Carol
Kirimunda, Samuel
Downing, Robert
Lutwama, Julian J
Mbidde, Edward K
Weyer, Jacqueline
Paweska, Janusz T
Joloba, Moses L
Wayengera, Misaki
author_facet Babirye, Peace
Musubika, Carol
Kirimunda, Samuel
Downing, Robert
Lutwama, Julian J
Mbidde, Edward K
Weyer, Jacqueline
Paweska, Janusz T
Joloba, Moses L
Wayengera, Misaki
author_sort Babirye, Peace
collection PubMed
description BACKGROUND: Ebolavirus 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. METHODS: In-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. RESULTS: Linear 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]. CONCLUSIONS: These 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3409-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-61711332018-10-10 Identity and validity of conserved B cell epitopes of filovirus glycoprotein: towards rapid diagnostic testing for Ebola and possibly Marburg virus disease Babirye, Peace Musubika, Carol Kirimunda, Samuel Downing, Robert Lutwama, Julian J Mbidde, Edward K Weyer, Jacqueline Paweska, Janusz T Joloba, Moses L Wayengera, Misaki BMC Infect Dis Research Article BACKGROUND: Ebolavirus 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. METHODS: In-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. RESULTS: Linear 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]. CONCLUSIONS: These 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3409-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-03 /pmc/articles/PMC6171133/ /pubmed/30285648 http://dx.doi.org/10.1186/s12879-018-3409-x Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Babirye, Peace
Musubika, Carol
Kirimunda, Samuel
Downing, Robert
Lutwama, Julian J
Mbidde, Edward K
Weyer, Jacqueline
Paweska, Janusz T
Joloba, Moses L
Wayengera, Misaki
Identity and validity of conserved B cell epitopes of filovirus glycoprotein: towards rapid diagnostic testing for Ebola and possibly Marburg virus disease
title Identity and validity of conserved B cell epitopes of filovirus glycoprotein: towards rapid diagnostic testing for Ebola and possibly Marburg virus disease
title_full Identity and validity of conserved B cell epitopes of filovirus glycoprotein: towards rapid diagnostic testing for Ebola and possibly Marburg virus disease
title_fullStr Identity and validity of conserved B cell epitopes of filovirus glycoprotein: towards rapid diagnostic testing for Ebola and possibly Marburg virus disease
title_full_unstemmed Identity and validity of conserved B cell epitopes of filovirus glycoprotein: towards rapid diagnostic testing for Ebola and possibly Marburg virus disease
title_short Identity and validity of conserved B cell epitopes of filovirus glycoprotein: towards rapid diagnostic testing for Ebola and possibly Marburg virus disease
title_sort identity and validity of conserved b cell epitopes of filovirus glycoprotein: towards rapid diagnostic testing for ebola and possibly marburg virus disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171133/
https://www.ncbi.nlm.nih.gov/pubmed/30285648
http://dx.doi.org/10.1186/s12879-018-3409-x
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