home > bioproject > PRJDB1886
identifier PRJDB1886
type bioproject
sra-study  DRP000370
organism Hepatitis C virus subtype 1b
title Genetic heterogeneity of hepatitis C virus in association with antiviral therapy determined by ultra-deep sequencing
description Background and Aims: The hepatitis C virus (HCV) invariably shows wide heterogeneity in infected patients, referred to as a quasispecies population. Conventional sequencing analyses for massive amounts of genetic information are limited due to the abundance of HCV quasispecies. Methods: Using a newly developed massive-parallel ultra-deep sequencing technique, we investigated the viral genetic heterogeneity in 27 chronic hepatitis C patients receiving peg-interferon (IFN) α2b plus ribavirin therapy. Results: Ultra-deep sequencing determined a total of more than 10 million nucleotides of the HCV genome, corresponding to a mean of more than 1000 clones in each specimen, and unveiled extremely high genetic heterogeneity in the genotype 1b HCV population. There was no significant difference in the level of viral complexity between early virologic responders and non-responders at baseline (p=0.39). Early virologic responders showed a significant reduction in the genetic complexity spanning all the viral genetic regions at the early phase of IFN administration (p=0.037). In contrast, non-virologic responders showed no significant changes in the level of viral quasispecies (p=0.12), indicating that very few viral clones are sensitive to IFN treatment. We also demonstrated that clones resistant to directly acting anti-HCV agents, such as viral protease and polymerase inhibitors, preexist with various abundances in treatment-naïve patients, suggesting the risk of the development of drug resistance against these agents. Conclusion: Use of the ultra-deep sequencing technology revealed massive genetic heterogeneity of HCV, which has important implications regarding the treatment response and outcome of antiviral therapy. none provided
data type DDBJ SRA Study
external link
sra-run  DRR000901DRR000902DRR000903DRR000904DRR000905DRR000906DRR000907DRR000908DRR000909DRR000910 More
sra-submission  DRA000366
biosample  SAMD00003293SAMD00003320SAMD00003314SAMD00003325SAMD00003299SAMD00003326SAMD00003327SAMD00003300SAMD00003311SAMD00003295 More
sra-study  DRP000370
sra-sample  DRS000580DRS000581DRS000582DRS000583DRS000584DRS000585DRS000586DRS000587DRS000588DRS000589 More
sra-experiment  DRX000551DRX000552DRX000553DRX000554DRX000555DRX000556DRX000557DRX000558DRX000559DRX000560 More
distribution JSONJSON-LD
status public
visibility unrestricted-access
dateCreated 2014-05-12T00:46:27+0000
dateModified 2014-05-12T00:46:27+0000
datePublished 2014-05-12T00:46:27+0000