@article{10360f17998b4ffb9ef70ae1c62e79a9,
title = "Genomic variability of within-host hepatitis C variants in acute infection",
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",
author = "{the InC3 Collaborative} and Chaturaka Rodrigo and Preston Leung and Lloyd, {Andrew R.} and Bull, {Rowena A.} and Fabio Luciani and Jason Grebely and Dore, {Gregory J.} and Tanya Applegate and Kimberly Page and Julie Bruneau and Cox, {Andrea L.} and William Osburn and Kim, {Arthur Y.} and Shoukry, {Naglaa H.} and Lauer, {Georg M.} and Lisa Maher and Janke Schinkel and Maria Prins and Margaret Hellard and Eltahla, {Auda A.}",
note = "Funding Information: The infrastructure for sharing of data and specimens in InC3 was funded by the National Institute on Drug Abuse (NIDA) R01DA031056. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of NIDA or the National Institutes of Health (NIH). Research support for the InC3 cohorts includes: the Netherlands National Institute for Public Health and the Environment to the Amsterdam Cohort Study (ACS); Baltimore Before and After Study (BBA) - National Institutes of Health (NIH U19 AI088791); Boston Acute HCV Study: transmission, immunity, outcomes network (BAHSTION) is funded under NIH NIAID U19 AI066345; ATAHC – NIDA RO1 DA 15999-01; HITS-p - National Health and Medical Research Council of Australia (NHMRC) - Project No. 222887, Partnership No. 1016351, Program Nos. 510488 and 1053206; HITS-c – UNSW Hepatitis C Vaccine Initiative and NHMRC Project Grant No. 630483; Networks/MIX – NHMRC Project Grants Nos. 331312 and 545891 and the Victorian Operational Infrastructure Support Programme (Department of Health, Victoria, Australia); HepCo - the Canadian Institutes of Health Research (MOP-103138 and MOP-106468; R{\'e}seau SIDA Maladies Infectieuses, Fonds de la Recherche du Qu{\'e}bec-Sant{\'e}); UFO – NIH R01 DA016017. The following InC3 investigators are funded by research fellowships: NHMRC, Australia – JG, MH, LM, GD, AL; Fonds de la Recherche du Qu{\'e}bec, Canada – JB and NS. Publisher Copyright: {\textcopyright} 2018 John Wiley & Sons Ltd",
year = "2019",
month = apr,
doi = "10.1111/jvh.13051",
language = "English (US)",
volume = "26",
pages = "476--484",
journal = "Journal of viral hepatitis",
issn = "1352-0504",
publisher = "Wiley-Blackwell",
number = "4",
}