Mapeamento imunoinformático de regiões conservadas da proteína hexon de adenovírus humano

• Autor(a) principal: Anjos, Déborah Carolina Carvalho dos
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/10560
• topic: Adenovírus humano; Alo-TCPH; Imunoinformática; Proteína hexon; Viremia; Human adenovirus; Allo-TCPH; Immunoinformatics; Hexon protein; viremia; CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA

Human Adenoviruses (HAdVs) are important infectious agents associated with high incidence, morbidity and mortality in immunocompromised patients, such as those undergoing allogeneic hematopoietic progenitor cell transplantation (allo-TCPH). HAdVs belong to the family Adenoviridae, genus Mastadenovirus, and further classified into seven species (A-G) and 103 genotypes, characterized so far. The HAdV capsid consists mainly of the hexon protein, which has four highly conserved regions (CR1 - 4) that are known for their immunogenic potential, being one of the main targets of the T and B cell-mediated anti-HAdV immune response. The aim of the present study was to perform the mapping of potentially immunogenic epitopes, located in the HAdV hexon CRs and to evaluate the HAdV infection in patients undergoing allo-TCPH. To this end, predictions of T and B cell epitopes and IFN-γ induction were performed, considering 101 HAdV genotypes with sequences available in databases. The most conserved and best classified epitopes were then selected by the prediction programs to perform the molecular docking analysis with HLA alleles of the study population, consisting of nine adult patients undergoing allo-TCPH. It was also carried out the HAdV research by TaqMan real-time polymerase chain reaction (qPCR) in the patient's serum samples. As a result, regions containing overlapping T and B cell epitopes were obtained and, based on immunoinformatics analysis (prediction and molecular docking), two peptides with high conservation and immunogenic potential were designed. Nine patients were positive for HAdV by qPCR TaqMan, with the average viral load found in the serum samples of the study population being 6.71x1011 CG / mL. The genomic sequencing of the positive samples returned sequences that showed 100% similarity with sequences of the HAdV C hexon protein, deposited in a database. The present study allowed the mapping of the main immunogenic regions located in the CRs of the HAdV hexon, as well as the construction of two peptides that will be used in future studies to evaluate the immune response of patients undergoing allo-TCPH, participating in the present study.