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. 2019 Apr;26(4):476-484.
doi: 10.1111/jvh.13051. Epub 2019 Jan 22.

Genomic variability of within-host hepatitis C variants in acute infection

Chaturaka Rodrigo  1 , Preston Leung  2 , Andrew R Lloyd  2 , Rowena A Bull  1   2 , Fabio Luciani  1   2 , Jason Grebely  2 , Gregory J Dore  2 , Tanya Applegate  2 , Kimberly Page  3 , Julie Bruneau  4 , Andrea L Cox  5 , William Osburn  5 , Arthur Y Kim  6 , Naglaa H Shoukry  4 , Georg M Lauer  6 , Lisa Maher  2 , Janke Schinkel  7   8 , Maria Prins  7   8 , Margaret Hellard  9   10   11   12 , Auda A Eltahla  1 ; InC3 Collaborative
Affiliations

Genomic variability of within-host hepatitis C variants in acute infection

Chaturaka Rodrigo et al. J Viral Hepat. 2019 Apr.

Abstract

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 SNPs 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 NS5B 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 IFNL3 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.

Keywords: IFNL3; InC3 study; Shannon entropy; hepatitis C virus; spontaneous clearance.

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Conflict of interest statement

Conflicts of interest: Authors have no conflicts of interest to declare regarding the content of this paper

Figures

Figure 1.
Figure 1.. Mean standardized genomic variability across different protein coding regions of the HCV genome in acute infection
Mean standardized genomic variability measured as Shannon Entropy (SE) are presented with standard deviations (whiskers) across 116 acute infection samples. Legends; a) red/dot: SE of all mutations, b) black/box: SE of synonymous mutations, c) blue/triangle: SE of non-synonymous mutations. The statistically significant differences were as follows; a) for total SE: E1 vs. NS4A, b) for non-synonymous SE: E1 vs. core, NS3, NS4A, NS4B and NS5A, c) for synonymous SE: none
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