| identifier |
PRJEB3123 |
| type |
bioproject |
| sameAs |
|
| organism |
|
| title |
Deep sequencing reveals mutagenic effects of ribavirin during monotherapy of HCV genotype 1-infected patients |
| description |
The preeminent mode of action of the broad-spectrum antiviral nucleoside ribavirin in the therapy of chronic hepatitis C is currently unresolved. Particularly under contest are possible mutagenic effects of ribavirin that may lead to viral extinction by lethal mutagenesis of the HCV genome. We applied ultra-deep sequencing to determine ribavirin-induced sequence changes in entire HCV genomes of patients treated with six-week ribavirin monotherapy in comparison to placebo. Analyses of viral nucleotide substitution rates revealed increased numbers of mutations and ribavirin-associated G-to-A and C-to-U transitions throughout the HCV coding region during all treatment intervals. Mutations and ribavirin-associated transitions were particularly enriched in the viral regions E1/E2 and NS5B. Ribavirin-associated transitions and ribavirin plasma concentrations of treated patients were highly correlated. We conclude that ribavirin exerts a significant mutagenic effect on the virus in patients with chronic hepatitis C by facilitating G-to-A and C-to-U nucleotide transitions. |
| data type |
Other
|
| organization |
|
| publication |
|
| properties ▽ |
{...}
|
| dbXrefs |
|
| distribution |
JSONJSON-LD
|
| Download |
|
| status |
public |
| visibility |
unrestricted-access |
| dateCreated |
2013-01-03T00:00:00Z |
| dateModified |
2013-01-03T00:00:00Z |
| datePublished |
2013-01-03T00:00:00Z |