Unknown

Dataset Information

0

Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes.


ABSTRACT: Hepatitis C virus (HCV) is a nonretroviral oncogenic RNA virus, which is frequently associated with hepatocellular carcinoma (HCC) and B cell lymphoma. We demonstrated here that acute and chronic HCV infection caused a 5- to 10-fold increase in mutation frequency in Ig heavy chain, BCL-6, p53, and beta-catenin genes of in vitro HCV-infected B cell lines and HCV-associated peripheral blood mononuclear cells, lymphomas, and HCCs. The nucleotide-substitution pattern of p53 and beta-catenin was different from that of Ig heavy chain in HCV-infected cells, suggesting two different mechanisms of mutation. In addition, the mutated protooncogenes were amplified in HCV-associated lymphomas and HCCs, but not in lymphomas of nonviral origin or HBV-associated HCC. HCV induced error-prone DNA polymerase zeta, polymerase iota, and activation-induced cytidine deaminase, which together, contributed to the enhancement of mutation frequency, as demonstrated by the RNA interference experiments. These results indicate that HCV induces a mutator phenotype and may transform cells by a hit-and-run mechanism. This finding provides a mechanism of oncogenesis for an RNA virus.

SUBMITTER: Machida K 

PROVIDER: S-EPMC384729 | BioStudies | 2004-01-01

REPOSITORIES: biostudies

Similar Datasets

2010-07-06 | GSE19665 | GEO
2010-07-06 | E-GEOD-19665 | ArrayExpress
2018-01-01 | S-EPMC5983165 | BioStudies
2016-01-01 | S-EPMC4970827 | BioStudies
2007-01-01 | S-EPMC3533246 | BioStudies
2020-01-01 | S-EPMC7202218 | BioStudies
2020-01-01 | S-EPMC7268324 | BioStudies
2012-01-01 | S-EPMC3446854 | BioStudies
2012-01-01 | S-EPMC3540370 | BioStudies
2019-01-01 | S-EPMC6689003 | BioStudies