| Autor: |
Stangherlin LM; Center for Natural Sciences and Humanities, Federal University of ABCSanto André, Brazil., de Paula FN; Center for Natural Sciences and Humanities, Federal University of ABCSanto André, Brazil.; Pasteur InstituteSão Paulo, Brazil., Icimoto MY; Department of Biophysics, Paulista Medical School, Federal University of São PauloSão Paulo, Brazil., Ruiz LGP; Medical School of São José do Rio PretoSão José do Rio Preto, Brazil., Nogueira ML; Medical School of São José do Rio PretoSão José do Rio Preto, Brazil., Braz ASK; Center for Natural Sciences and Humanities, Federal University of ABCSanto André, Brazil., Juliano L; Department of Biophysics, Paulista Medical School, Federal University of São PauloSão Paulo, Brazil., da Silva MCC; Center for Natural Sciences and Humanities, Federal University of ABCSanto André, Brazil. |
| Abstrakt: |
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. |
