Caracterização dos subtipos e quasispecies do vírus da hepatite C e resposta imune em pacientes renais crônicos

Abstract

Hepatitis C is a major public health problem due to the high prevalence of infection in the population. HCV has antigenic regions that activate a strong innate and adaptive immune response. However, failures occur during the defense in the initial infection and approximately 80% of patients develop a chronic disease . Only 15-20% of infected patients can suppress the virus and progress to recovery. The mechanisms by which HCV evades the immune system is very diverse as: nucleotides variability, inhibiting the HLA expression, blocking apoptosis and antibody production. This study aimed to characterize HCV subtypes and its variants (quasispecies) and evaluate the immune response in samples obtained from patients with chronic renal failure on hemodialysis. To develop this work we used the techniques of EPLD-PCR and 454 sequencing for analysis of quasispecies. It was made immunophenotyping of peripheral blood leukocytes by flow cytometry and cytokine ELISA. Our results showed that among patients RC genotype / subtype with the highest prevalence were 1a, 1b and 3a, and the circulating viral population in each patient consists of about 13 quasispecies. The phylogenetic analysis of the quasispecies demonstrated cases of nosocomial transmission, between two groups of patients the variants found suggested the same source of infection and a third group of patients presented variants with a closer relationship. CR patients showed a decrease in LTCD4 when compared to HCV-infected chronic renal patients. Through correlation analysis, it was observed that IL-4 had a positive influence on the formation of quasispecies, while IL-10 seems to be related to the decrease in quasispecies. The results of the present study suggest that the hemodialysis procedure contributes to inducing HCV to undergo a wide viral diversity to stimulate immune system escape mechanisms and thus induce chronic infection and that it can also be a nosocomial transmission route.