Molecular Characterization of Hepatite C Virus from renal chronic disease patients under hemodialysis

• Grant number: 12/18168-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2013
• End date: August 31, 2014
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Isabel Maria Vicente Guedes de Carvalho Mello
• Grantee: Rafael Alves da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The difficulties related to diagnosis and treatment against hepatitis C virus (HCV) infection has stimulated researches in drugs development area. New treatments have as main feature the virus direct inhibition by preventing the function of proteins scents in its replication. The new treatments unique mechanism of function makes the knowledge of molecular characteristics extreme important. Patients with renal impairment in hemodialysis sessions have different characteristics of patients with normal renal function. Ribavirin (RBV) is not well absorbed by the system and use of interferon is restricted to conventional (INFC). The risk of infection during hemodialysis and the difference of selective pressure exerted by the different treatments regimens raise questions about the virus molecular characteristics in these patients. The aim of this study is to characterize molecular variants of HCV circulating in patients with chronic kidney disease on hemodialysis compared with variants of HCV patients with normal renal function. Two groups of patients will be analyzed in this work. The first group will have 100 patients with chronic HCV infection and chronic kidney disease under hemodialysis for at least 1 year and the second group will include 100 patients with chronic HCV infection without impaired renal function. Viral RNA will be extracted from patients' sera, amplified and sequenced in the regions NS3 (~ 620nt) and NS5B (~ 800nt). After validation and alignment a phylogenetic analysis of distance and likelihood will be performed for genotyping. A search for conserved regions through calculation of entropy and conserved motifs, search for mutations conferring resistance to new treatments as well as analysis of the outcome of phylogeny in search branching pattern between the two groups of patients will be realized. After this work it is expected a better understanding of molecular characteristics from HCV variants in patients with chronic kidney disease, identify possible genetic polymorphisms and characteristic patterns of these two groups.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA SILVA, RAFAEL ALVES; VICENTE GUEDES DE CARVALHO, ISABEL MARIA; ADUM DE MATOS, RENATA PRANDINI; TOMONARI YAMASAKI, LILIAN HIROMI; BITTAR, CINTIA; RAHAL, PAULA; GOMES JARDIM, ANA CAROLINA. Evidence of bottleneck effect on hepatitis C virus transmission between a couple under interferon based therapy. INFECTION GENETICS AND EVOLUTION, v. 47, p. 87-93, JAN 2017. (10/06156-4, 12/18168-2)

DE CARVALHO, ISABEL M. V. G.; ALVES, RAFAEL; VASCONCELOS-MEDEIROS DE SOUZA, POLYANA A.; DA SILVA, EDVALDO F.; MAZO, DANIEL; CARRILHO, FLAIR J.; QUEIROZ, ARTUR T. L.; PESSOA, MARIO G.. Protease Inhibitor Resistance Mutations in Untreated Brazilian Patients Infected with HCV: Novel Insights about Targeted Genotyping Approaches. Journal of Medical Virology, v. 86, n. 10, p. 1714-1721, OCT 2014. (12/18168-2, 09/14277-9)

DA SILVA, RAFAEL ALVES; TODAO, JARDELINA DE SOUZA; KAMITANI, FERNANDO LUIZ; BENEDITO SILVA, ANTONIO EDUARDO; DE CARVALHO-FILHO, ROBERTO JOSE; CARDOSO GOMES FERRAZ, MARIA LUCIA; VICENTE GUEDES DE CARVALHO, ISABEL MARIA. Molecular characterization of hepatitis C virus in end-stage renal disease patients under hemodialysis. Journal of Medical Virology, v. 90, n. 3, p. 537-544, MAR 2018. (12/18168-2)