Molecular characterization of hepatitis C virus in end-stage renal disease patients under hemodialysis

Author(s)

da Silva, Rafael Alves ^{[1, 2]} ; Todao, Jardelina de Souza ^[1] ; Kamitani, Fernando Luiz ^[2] ; Benedito Silva, Antonio Eduardo ^{[1, 3]} ; de Carvalho-Filho, Roberto Jose ^{[1, 3]} ; Cardoso Gomes Ferraz, Maria Lucia ^{[1, 3]} ; Vicente Guedes de Carvalho, Isabel Maria ^{[1, 2]}

Affiliation

^[1] Univ Fed Sao Paulo, Lab Hepatol Mol Aplicada LHeMA, UNIFESP, Dept Gastroenterol, Unidade Hepatol, Sao Paulo - Brazil

^[2] Inst Butantan, Lab Parasitol, Ave Vital Brasil 1500, BR-05503900 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Gastroenterol, Unidade Hepatol, UNIFESP, Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Medical Virology; v. 90, n. 3, p. 537-544, MAR 2018.
• Web of Science Citations: 2

Abstract

New direct-acting antiviral (DAA) agents are in development or already approved for the treatment of chronic hepatitis C virus (HCV) infection. The effectiveness of these drugs is related to the previous existence of resistant variants. Certain clinical conditions can allow changes in immunological characteristics of the host and even modify genetic features of viral populations. The aim of this study was to perform HCV molecular characterization from samples of end-stage renal disease patients on hemodialysis (ESRD-HD). Nested PCR and Sanger sequencing were used to obtain genetic information from the NS5B partial region of a cohort composed by 86 treatment-naive patients. Genomic sequences from the Los Alamos databank were employed for comparative analysis. Bioinformatics methodologies such as phylogenetic reconstructions, informational entropy, and mutation analysis were used to analyze datasets separated by geographical location, HCV genotype, and renal function status. ESRD-HD patients presented HCV genotypes 1a (n=18), 1b (n=16), 2a (n=2), 2b (n=2), and 3a (n=4). Control subjects were infected with genotypes 1a (n=11), 1b (n=21), 2b (n=4), and 3a (n=8). Dataset phylogenetic reconstruction separated HCV subtype 1a into two distinct clades. The entropy analysis from the ESRD-HD group revealed two amino acid positions related to an epitope for cytotoxic T lymphocytes and T helper cells. Genotype 1a was found to be more diverse than subtype 1b. Also, genotype 1a ERSD-HD patients had a higher mean of amino acids changes in comparison to control group patients. The identification of specific mutations on epitopes and high genetic diversity within the NS5B HCV partial protein in hemodialysis patients can relate to host immunological features and geographical distribution patterns. This genetic diversity can affect directly the new DAA's resistance mechanisms. (AU)

• FAPESP's process: 12/18168-2 - Molecular Characterization of Hepatite C Virus from renal chronic disease patients under hemodialysis
• Grantee: Rafael Alves da Silva
• Support Opportunities: Scholarships in Brazil - Master