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

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...

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Bibliographic Details
Published in:	Journal of medical virology Vol. 90; no. 3; pp. 537 - 544
Main Authors:	Alves da Silva, Rafael, de Souza Todão, Jardelina, Kamitani, Fernando Luiz, Silva, Antonio Eduardo Benedito, de Carvalho‐Filho, Roberto José, Ferraz, Maria Lucia Cardoso Gomes, de Carvalho, Isabel Maria Vicente Guedes
Format:	Journal Article
Language:	English
Published:	United States Wiley Subscription Services, Inc 01-03-2018
Subjects:	Amino acids Antiviral agents Antiviral Agents - therapeutic use Bioinformatics Chronic infection Comparative analysis Computational Biology Cytotoxicity Dialysis Drug Resistance, Viral Drugs End-stage renal disease Entropy Epitopes evolution Evolution, Molecular Gene sequencing Genetic diversity genetic variability Genetic Variation genetics Genotype Genotypes Geographical distribution Helper cells Hemodialysis Hepacivirus - classification Hepacivirus - genetics Hepatitis Hepatitis C hepatitis C virus Hepatitis C, Chronic - drug therapy Humans Immunology Kidney diseases Kidney Failure, Chronic - virology Lymphocytes Lymphocytes T Mutation Patients Phylogenetics Phylogeny Polymerase Chain Reaction Population genetics Renal Dialysis Renal function Sequence Analysis, DNA Viral Nonstructural Proteins - genetics Virology virus classification Viruses hepatitis C virus mutation genetics evolution virus classification genetic variability
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Summary:	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‐naïve 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0146-6615 1096-9071
DOI:	10.1002/jmv.24976