A20 Enhances the Expression of the Proto-Oncogene C-Myc by Downregulating TRAF6 Ubiquitination after ALV-A Infection

Viruses. 2022 Oct 7;14(10):2210. doi: 10.3390/v14102210.

Abstract

Hens infected with avian leukosis virus subgroup A (ALV-A) experience stunted growth, immunosuppression, and potentially, lymphoma development. According to past research, A20 can both promote and inhibit tumor growth. In this study, DF-1 cells were infected with ALV-A rHB2015012, and Gp85 expression was measured at various time points. A recombinant plasmid encoding the chicken A20 gene and short hairpin RNA targeting chicken A20 (A20-shRNA) was constructed and transfected into DF-1 cells to determine the effect on ALV-A replication. The potential signaling pathways of A20 were explored using bioinformatics prediction, co-immunoprecipitation, and other techniques. The results demonstrate that A20 and ALV-A promoted each other after ALV-A infection of DF-1 cells, upregulated A20, inhibited TRAF6 ubiquitination, and promoted STAT3 phosphorylation. The phosphorylated-STAT3 (p-STAT3) promoted the expression of proto-oncogene c-myc, which may lead to tumorigenesis. This study will help to further understand the tumorigenic process of ALV-A and provide a reference for preventing and controlling ALV.

Keywords: ALV-A; STAT3; TRAF6; c-myc; chicken A20; tumorigenic mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avian Leukosis Virus* / genetics
  • Avian Leukosis*
  • Chickens / genetics
  • Female
  • Poultry Diseases*
  • Proto-Oncogenes
  • RNA, Small Interfering / genetics
  • TNF Receptor-Associated Factor 6 / genetics
  • Ubiquitination

Substances

  • TNF Receptor-Associated Factor 6
  • RNA, Small Interfering

Grants and funding

This research was funded by National Nature Science Foundation of China (No. 31972646), Scientific Research Project of Education Department of Hubei Province (B2019028), and Scientific Research Project of Jingzhou City (2020CB21-31), Hubei Nature Province Science Foundation of China (2021CFB173).