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J Viral Hepat. 2018 Dec 22. doi: 10.1111/jvh.13051. [Epub ahead of print]

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

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School of Medical Sciences, UNSW, Sydney, New South Wales, Australia.
The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.
University of New Mexico, Albuquerque, New Mexico.
Centre de Recherche du Centre hospitalier de l', Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
Johns Hopkins Medical Institutions, Baltimore, Maryland.
Harvard Medical School, Boston, Massachusetts.
Academic Medical Center, Amsterdam, The Netherlands.
GGD Public Health Service of Amsterdam, Amsterdam, The Netherlands.
Burnet Institute, Melbourne, Victoria, Australia.
Monash University, Melbourne, Victoria, Australia.
Alfred Hospital, Melbourne, Victoria, Australia.
Doherty Institute and Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.


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.


IFNL3; InC3 study; Shannon entropy; hepatitis C virus; spontaneous clearance


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