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Positively Selected Sites at HCMV gB Furin Processing Region and Their Effects in Cleavage Efficiency
Human cytomegalovirus is a ubiquitous infectious agent that affects mainly immunosuppressed, fetuses, and newborns. The virus has several polymorphic regions, in particular in the envelope glycoproteins. The UL55 gene encodes the glycoprotein B that has a variable region, containing a furin cleavage...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441137/ https://www.ncbi.nlm.nih.gov/pubmed/28588572 http://dx.doi.org/10.3389/fmicb.2017.00934 |
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author | Stangherlin, Lucas M. de Paula, Felipe N. Icimoto, Marcelo Y. Ruiz, Leonardo G. P. Nogueira, Maurício L. Braz, Antônio S. K. Juliano, Luiz da Silva, Maria C. C. |
author_facet | Stangherlin, Lucas M. de Paula, Felipe N. Icimoto, Marcelo Y. Ruiz, Leonardo G. P. Nogueira, Maurício L. Braz, Antônio S. K. Juliano, Luiz da Silva, Maria C. C. |
author_sort | Stangherlin, Lucas M. |
collection | PubMed |
description | Human cytomegalovirus is a ubiquitous infectious agent that affects mainly immunosuppressed, fetuses, and newborns. The virus has several polymorphic regions, in particular in the envelope glycoproteins. The UL55 gene encodes the glycoprotein B that has a variable region, containing a furin cleavage site and according to the variability different genotypes are characterized. Here we investigated variability and existence of selective pressure on the UL55 variable region containing the furin cleavage site in 213 clinical sequences from patients worldwide. We showed the occurrence of positive selective pressure on gB codons 461 and 462, near the furin cleavage site. Cleavage analysis of synthesized peptides demonstrated that most mutations confer better cleavage by furin, suggesting that evolution is acting in order to increase the efficiency cleavage and supporting the hypothesis that gB processing is important in the host. We also demonstrated that peptides containing sequences, that characterize genotypes gB2 and 3, are differentially cleaved by furin. Our data demonstrate for the first time that variability in the cleavage site is related to degree of gB processing by furin. |
format | Online Article Text |
id | pubmed-5441137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54411372017-06-06 Positively Selected Sites at HCMV gB Furin Processing Region and Their Effects in Cleavage Efficiency Stangherlin, Lucas M. de Paula, Felipe N. Icimoto, Marcelo Y. Ruiz, Leonardo G. P. Nogueira, Maurício L. Braz, Antônio S. K. Juliano, Luiz da Silva, Maria C. C. Front Microbiol Microbiology Human cytomegalovirus is a ubiquitous infectious agent that affects mainly immunosuppressed, fetuses, and newborns. The virus has several polymorphic regions, in particular in the envelope glycoproteins. The UL55 gene encodes the glycoprotein B that has a variable region, containing a furin cleavage site and according to the variability different genotypes are characterized. Here we investigated variability and existence of selective pressure on the UL55 variable region containing the furin cleavage site in 213 clinical sequences from patients worldwide. We showed the occurrence of positive selective pressure on gB codons 461 and 462, near the furin cleavage site. Cleavage analysis of synthesized peptides demonstrated that most mutations confer better cleavage by furin, suggesting that evolution is acting in order to increase the efficiency cleavage and supporting the hypothesis that gB processing is important in the host. We also demonstrated that peptides containing sequences, that characterize genotypes gB2 and 3, are differentially cleaved by furin. Our data demonstrate for the first time that variability in the cleavage site is related to degree of gB processing by furin. Frontiers Media S.A. 2017-05-23 /pmc/articles/PMC5441137/ /pubmed/28588572 http://dx.doi.org/10.3389/fmicb.2017.00934 Text en Copyright © 2017 Stangherlin, de Paula, Icimoto, Ruiz, Nogueira, Braz, Juliano and da Silva. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Stangherlin, Lucas M. de Paula, Felipe N. Icimoto, Marcelo Y. Ruiz, Leonardo G. P. Nogueira, Maurício L. Braz, Antônio S. K. Juliano, Luiz da Silva, Maria C. C. Positively Selected Sites at HCMV gB Furin Processing Region and Their Effects in Cleavage Efficiency |
title | Positively Selected Sites at HCMV gB Furin Processing Region and Their Effects in Cleavage Efficiency |
title_full | Positively Selected Sites at HCMV gB Furin Processing Region and Their Effects in Cleavage Efficiency |
title_fullStr | Positively Selected Sites at HCMV gB Furin Processing Region and Their Effects in Cleavage Efficiency |
title_full_unstemmed | Positively Selected Sites at HCMV gB Furin Processing Region and Their Effects in Cleavage Efficiency |
title_short | Positively Selected Sites at HCMV gB Furin Processing Region and Their Effects in Cleavage Efficiency |
title_sort | positively selected sites at hcmv gb furin processing region and their effects in cleavage efficiency |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441137/ https://www.ncbi.nlm.nih.gov/pubmed/28588572 http://dx.doi.org/10.3389/fmicb.2017.00934 |
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