3 research outputs found
Analýza zkřížené sérologické reaktivity protilátek proti variantám BK polyomaviru
BK polyomavirus (BKPyV), which asymptomatically infects about 80 % of the human population, can reactivate in immunosuppressed patients after kidney transplantation and cause nephropathy. In the European population, there are predominantly two BKPyV sub- types, BKPyV-I and BKPyV-IV, which behave as different serotypes. Recipients who receive a kidney from a donor positive for a different subtype are at a greater risk of graft rejection. So far, it is impossible to distinguish between these two subtypes using a serological ELISA test as serum antibodies against these two subtypes cross-react. This work aimed to iden- tify epitopes on the major antigenic protein VP1, which are responsible for the binding of cross-reacting and/or subtype-specific antibodies. The identification of such epitopes could further lead to improvement in pre-transplant diagnostics and better management of pati- ents after transplantation. Therefore, two types of antigens composed of the VP1 protein of the BKPyV-IV subtype with introduced mutations characteristic of BKPyV-I in the DE and EF loops of VP1 were prepared and tested using an antigen competition assay with a panel of human sera. The results showed that the DE loop region is an immunogenic epitope that binds specific antibodies for BKPyV subtype I. Conversely, a mutation in...BK polyomavirus (BKPyV), který asymptomaticky infikuje zhruba 80 % lidské populace, se může reaktivovat u imunosuprimovaných pacientů po transplantaci ledviny a způsobit nefropatii. V evropské populaci kolují nejčastěji dva subtypy BKPyV, BKPyV-I a BKPyV- IV, které se chovají jako odlišné sérotypy. Ukazuje se, že recipienti, kteří přijímají ledvinu od dárce pozitivního na jiný BKPyV subtyp, mají větší riziko odmítnutí štěpu. Jen pomocí sérologického testu ELISA ale nelze rozhodnout, zda je pacient infikován subtypem BKPyV-I či BKPyV-IV, jelikož protilátková odpověď proti těmto dvěma subtypům je zkřížená. Tato práce si kladla za cíl identifikovat epitopy na hlavním antigenním proteinu VP1, které jsou zodpovědné za vazbu křížově reagujících a/nebo subtypově specifických protilátek. Identifi- kace takových epitopů by mohla dále vést ke zlepšení pretransplantační diagnostiky a lepšímu managementu pacientů po transplantaci. Proto byly připraveny dva typy antigenů složené z VP1 proteinu subtypu BKPyV-IV se zavedenými mutacemi charakteristickými pro BKPyV-I v DE a EF smyčce VP1, které byly otestovány pomocí kompetiční eseje na panelu lidských sér. Výsledky ukázaly, že oblast DE smyčky je imunogenní epitop, který váže specifické proti- látky pro subtyp I. Naopak mutace v EF smyčce porušily epitop, který je obecně...Katedra genetiky a mikrobiologieDepartment of Genetics and MicrobiologyFaculty of SciencePřírodovědecká fakult
Macropinocytosis in viral infection
Department of Genetics and MicrobiologyKatedra genetiky a mikrobiologiePřírodovědecká fakultaFaculty of Scienc
Analysis of serological cross-reactivity between antibodies against BK polyomavirus variants
BK polyomavirus (BKPyV), which asymptomatically infects about 80 % of the human population, can reactivate in immunosuppressed patients after kidney transplantation and cause nephropathy. In the European population, there are predominantly two BKPyV sub- types, BKPyV-I and BKPyV-IV, which behave as different serotypes. Recipients who receive a kidney from a donor positive for a different subtype are at a greater risk of graft rejection. So far, it is impossible to distinguish between these two subtypes using a serological ELISA test as serum antibodies against these two subtypes cross-react. This work aimed to iden- tify epitopes on the major antigenic protein VP1, which are responsible for the binding of cross-reacting and/or subtype-specific antibodies. The identification of such epitopes could further lead to improvement in pre-transplant diagnostics and better management of pati- ents after transplantation. Therefore, two types of antigens composed of the VP1 protein of the BKPyV-IV subtype with introduced mutations characteristic of BKPyV-I in the DE and EF loops of VP1 were prepared and tested using an antigen competition assay with a panel of human sera. The results showed that the DE loop region is an immunogenic epitope that binds specific antibodies for BKPyV subtype I. Conversely, a mutation in..