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Genomic variability of within‐host hepatitis C variants in acute infection
Author(s) -
Rodrigo Chaturaka,
Leung Preston,
Lloyd Andrew R.,
Bull Rowena A.,
Luciani Fabio,
Grebely Jason,
Dore Gregory J.,
Applegate Tanya,
Page Kimberly,
Bruneau Julie,
Cox Andrea L.,
Osburn William,
Kim Arthur Y.,
Shoukry Naglaa H.,
Lauer Georg M.,
Maher Lisa,
Schinkel Janke,
Prins Maria,
Hellard Margaret,
Eltahla Auda A.
Publication year - 2019
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.13051
Subject(s) - nonsynonymous substitution , biology , viral quasispecies , genetics , single nucleotide polymorphism , virology , viral load , genotype , snp , genetic variation , hepatitis c virus , virus , genome , gene
Summary Interactions between the host immune system and the viral variants determine persistence of hepatitis C virus ( HCV ) infection after the acute phase of infection. This study describes the genetic variability of within‐host HCV viral variants in acute infection and correlates it with host‐ and virus‐related traits and infection outcome. Next generation sequence data (Illumina, MiSeq platform) of viral genomes from 116 incident acute infections (within 180 days of infection) were analysed to determine all the single nucleotide polymorphism ( SNP ) frequencies above a threshold of 0.1%. The variability of the SNP s for the full open reading frame of the genome as well as for each protein coding region were compared using mean standardized Shannon entropy ( SE ) values calculated separately for synonymous and nonsynonymous mutations. The envelope glycoproteins regions (E1 and E2) had the highest SE values (indicating greater variability) followed by the NS 5B region. Nonsynonymous mutations rather than synonymous mutations were the main contributors to genomic variability in acute infection. The mean difference of Shannon entropy was also compared between subjects after categorizing the samples according to host and virus‐related traits. Host IFNL 3 allele CC polymorphism at rs12979860 (vs others) and viral genotype 1a (vs 3a) were associated with higher genomic variability across the viral open reading frame. Time since infection, host gender or continent of origin was not associated with the viral genomic variability. Viral genomic variability did not predict spontaneous clearance.