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The MYC , TERT , and ZIC1 Genes Are Common Targets of Viral Integration and Transcriptional Deregulation in Avian Leukosis Virus Subgroup J-Induced Myeloid Leukosis
- Source :
- Journal of Virology. 88:3182-3191
- Publication Year :
- 2014
- Publisher :
- American Society for Microbiology, 2014.
-
Abstract
- The integration of retroviruses into the host genome following nonrandom genome-wide patterns may lead to the deregulation of gene expression and oncogene activation near the integration sites. Slow-transforming retroviruses have been widely used to perform genetic screens for the identification of genes involved in cancer. To investigate the involvement of avian leukosis virus subgroup J (ALV-J) integration in myeloid leukosis (ML) in chickens, we utilized an ALV-J insertional identification platform based on hybrid capture target enrichment and next-generation sequencing (NGS). Using high-definition mapping of the viral integration sites in the chicken genome, 241 unique insertion sites were obtained from six different ALV-J-induced ML samples. On the basis of previous statistical definitions, MYC , TERT , and ZIC1 genes were identified as common insertion sites (CIS) of provirus integration in tumor cells; these three genes have previously been shown to be involved in the malignant transformation of different human cell types. Compared to control samples, the expression levels of all three CIS genes were significantly upregulated in chicken ML samples. Furthermore, they were frequently, but not in all field ML cases, deregulated at the mRNA level as a result of ALV-J infection. Our findings contribute to the understanding of the relationship between multipathotypes associated with ALV-J infection and the molecular background of tumorigenesis. IMPORTANCE ALV-Js have been successfully eradicated from chicken breeding flocks in the poultry industries of developed countries, and the control and eradication of ALV-J in China are now progressing steadily. To further study the pathogenesis of ALV-J infections, it will be necessary to elucidate the in vivo viral integration and tumorigenesis mechanism. In this study, 241 unique insertion sites were obtained from six different ALV-J-induced ML samples. In addition, MYC , TERT , and ZIC1 genes were identified as the CIS of ALV-J in tumor cells, which might be a putative “driver” for the activation of the oncogene. In addition, the CIS genes showed deregulated expression compared to nontumor samples. These results have potentially important implications for the mechanism of viral carcinogenesis.
- Subjects :
- Transcription, Genetic
Virus Integration
Molecular Sequence Data
Immunology
Biology
medicine.disease_cause
Microbiology
Genome
Transformation and Oncogenesis
Malignant transformation
Avian Proteins
Proto-Oncogene Proteins c-myc
Virology
medicine
Animals
Telomerase
Gene
Poultry Diseases
Genetics
Avian Leukosis Virus
Oncogene
Provirus
Up-Regulation
Avian Leukosis
Gene Expression Regulation
Insect Science
Carcinogenesis
Chickens
Transcription Factors
Genetic screen
Subjects
Details
- ISSN :
- 10985514 and 0022538X
- Volume :
- 88
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....ea0ed17c10d0a8e514a5ac8644bbfa45
- Full Text :
- https://doi.org/10.1128/jvi.02995-13