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MON-522 In Silico Analysis of Polymorphism rs2228638 in Neuropillin-1 Demonstrated That This Variant May Hinder EBV Entry into Epithelial Cells

The Epstein-Barr virus (EBV) is the first herpesvirus identified to be associated with human cancers and our group has demonstrated its association to thyroid cancer. It infects the vast majority of the world population causing latent and persistent infection, interfering in the metabolism of the ho...

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Autores principales: Teixeira, Elisangela Souza, Almeida, Jacqueline Fatima Martins, Teodoro, Larissa, Peres, Karina Colombera, Bufalo, Natassia Elena, Ward, Laura Sterian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207861/
http://dx.doi.org/10.1210/jendso/bvaa046.1842
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author Teixeira, Elisangela Souza
Almeida, Jacqueline Fatima Martins
Teodoro, Larissa
Peres, Karina Colombera
Bufalo, Natassia Elena
Ward, Laura Sterian
author_facet Teixeira, Elisangela Souza
Almeida, Jacqueline Fatima Martins
Teodoro, Larissa
Peres, Karina Colombera
Bufalo, Natassia Elena
Ward, Laura Sterian
author_sort Teixeira, Elisangela Souza
collection PubMed
description The Epstein-Barr virus (EBV) is the first herpesvirus identified to be associated with human cancers and our group has demonstrated its association to thyroid cancer. It infects the vast majority of the world population causing latent and persistent infection, interfering in the metabolism of the host cells and triggering tumorigenic processes. Neuropillin-1 (NRP-1) is a type I transmembrane glycoprotein distributed on the cell surface of the virus, and considered vital for tumorigenesis. It has been demonstrated that EBV infection was increased by NRP1 expression. However, a conformational alteration of NRP1 could interfere with virus internalization into epithelial cells. The rs2228638 polymorphism of NRP1 may modify the molecule tridimensional configuration. In order to better understand the role of this polymorphism, based on NCBI dbSNP and UniProt databases, we evaluated the effect of the amino acid change in the protein structure using bioinformatics tools including SIFT, Align GVGD, PolyPhen-2, SNAP, PANTHER, PredictSNP, nsSNPAnalyzer, PROVEAN, SNP&GO, PMut and MuPRO. PANTHER prediction indicated that the polymorphic variant could produce a change in function. MuPRO indicated that the amino acid exchange produced by the polymorphism decreases protein stability. However, none of these tools showed conformational alteration. In conclusion, the presence of the rs2228638 polymorphism of NRP-1 may cause functional but not morphological changes that hinder EBV entry into the epithelial cells.
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spelling pubmed-72078612020-05-13 MON-522 In Silico Analysis of Polymorphism rs2228638 in Neuropillin-1 Demonstrated That This Variant May Hinder EBV Entry into Epithelial Cells Teixeira, Elisangela Souza Almeida, Jacqueline Fatima Martins Teodoro, Larissa Peres, Karina Colombera Bufalo, Natassia Elena Ward, Laura Sterian J Endocr Soc Thyroid The Epstein-Barr virus (EBV) is the first herpesvirus identified to be associated with human cancers and our group has demonstrated its association to thyroid cancer. It infects the vast majority of the world population causing latent and persistent infection, interfering in the metabolism of the host cells and triggering tumorigenic processes. Neuropillin-1 (NRP-1) is a type I transmembrane glycoprotein distributed on the cell surface of the virus, and considered vital for tumorigenesis. It has been demonstrated that EBV infection was increased by NRP1 expression. However, a conformational alteration of NRP1 could interfere with virus internalization into epithelial cells. The rs2228638 polymorphism of NRP1 may modify the molecule tridimensional configuration. In order to better understand the role of this polymorphism, based on NCBI dbSNP and UniProt databases, we evaluated the effect of the amino acid change in the protein structure using bioinformatics tools including SIFT, Align GVGD, PolyPhen-2, SNAP, PANTHER, PredictSNP, nsSNPAnalyzer, PROVEAN, SNP&GO, PMut and MuPRO. PANTHER prediction indicated that the polymorphic variant could produce a change in function. MuPRO indicated that the amino acid exchange produced by the polymorphism decreases protein stability. However, none of these tools showed conformational alteration. In conclusion, the presence of the rs2228638 polymorphism of NRP-1 may cause functional but not morphological changes that hinder EBV entry into the epithelial cells. Oxford University Press 2020-05-08 /pmc/articles/PMC7207861/ http://dx.doi.org/10.1210/jendso/bvaa046.1842 Text en © Endocrine Society 2020. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Thyroid
Teixeira, Elisangela Souza
Almeida, Jacqueline Fatima Martins
Teodoro, Larissa
Peres, Karina Colombera
Bufalo, Natassia Elena
Ward, Laura Sterian
MON-522 In Silico Analysis of Polymorphism rs2228638 in Neuropillin-1 Demonstrated That This Variant May Hinder EBV Entry into Epithelial Cells
title MON-522 In Silico Analysis of Polymorphism rs2228638 in Neuropillin-1 Demonstrated That This Variant May Hinder EBV Entry into Epithelial Cells
title_full MON-522 In Silico Analysis of Polymorphism rs2228638 in Neuropillin-1 Demonstrated That This Variant May Hinder EBV Entry into Epithelial Cells
title_fullStr MON-522 In Silico Analysis of Polymorphism rs2228638 in Neuropillin-1 Demonstrated That This Variant May Hinder EBV Entry into Epithelial Cells
title_full_unstemmed MON-522 In Silico Analysis of Polymorphism rs2228638 in Neuropillin-1 Demonstrated That This Variant May Hinder EBV Entry into Epithelial Cells
title_short MON-522 In Silico Analysis of Polymorphism rs2228638 in Neuropillin-1 Demonstrated That This Variant May Hinder EBV Entry into Epithelial Cells
title_sort mon-522 in silico analysis of polymorphism rs2228638 in neuropillin-1 demonstrated that this variant may hinder ebv entry into epithelial cells
topic Thyroid
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207861/
http://dx.doi.org/10.1210/jendso/bvaa046.1842
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