Positively Selected Sites at HCMV gB Furin Processing Region and Their Effects in Cleavage Efficiency

dc.contributor.authorStangherlin, Lucas M.
dc.contributor.authorde Paula, Felipe N.
dc.contributor.authorIcimoto, Marcelo Y. [UNIFESP]
dc.contributor.authorRuiz, Leonardo G. P.
dc.contributor.authorNogueira, Mauricio L.
dc.contributor.authorBraz, Antonio S. K.
dc.contributor.authorJuliano, Luiz [UNIFESP]
dc.contributor.authorda Silva, Maria C. C.
dc.description.abstractHuman 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.en
dc.description.affiliationFed Univ ABC, Ctr Nat Sci & Humanities, Santo Andre, Brazil
dc.description.affiliationPasteur Inst, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Paulista Med Sch, Dept Biophys, Sao Paulo, Brazil
dc.description.affiliationMed Sch Sao Jose Do Rio Preto, Sao Jose Do Rio Preto, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Paulista Med Sch, Dept Biophys, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP
dc.description.sponsorshipIDFAPESP: 2013/14215-9
dc.identifier.citationFrontiers In Microbiology. Lausanne, v. 8, p. -, 2017.
dc.publisherFrontiers Media Sa
dc.relation.ispartofFrontiers In Microbiology
dc.rightsAcesso aberto
dc.subjecthuman cytomegalovirusen
dc.subjectglycoprotein Ben
dc.subjectselective pressureen
dc.subjectfurin cleavageen
dc.subjectgB genotypesen
dc.titlePositively Selected Sites at HCMV gB Furin Processing Region and Their Effects in Cleavage Efficiencyen