Molecular cloning and functional characterization of duck TYK2

Dev Comp Immunol. 2020 Jan:102:103474. doi: 10.1016/j.dci.2019.103474. Epub 2019 Aug 20.

Abstract

Tyrosine kinase 2 (TYK2), a member of Janus kinase family, has been identified as a crucial protein in signal transduction initiated by interferons or interleukins in mammals. However, the function of avian TYK2 in innate immune response remains largely unknown. In this study, the full-length duck TYK2 (duTYK2) cDNA was cloned for the first time, which encoded a putative protein of 1187 amino acid residues and showed the high sequence similarity with bald eagle, crested ibis, and white-tailed tropicbird TYK2s. The duTYK2 was widely expressed in all examined tissues of healthy ducks and showed diffuse cytoplasmic localization in duck embryo fibroblasts (DEFs). Overexpression of duTYK2 significantly enhanced ISRE promoter activity and induced the expression of viperin, PKR, 2',5'-OAS, Mx and ZAP in DEFs. The C-terminal kinase domain of duTYK2 is essential for duTYK2-mediated ISRE promoter activation. Furthermore, knockdown of duTYK2 dramatically decreased duck Tembusu virus (DTMUV)-, duck enteritis virus (DEV)-, poly(I:C)- or poly(dA:dT)-induced ISRE promoter activation. Additionally, duTYK2 expression exhibited antiviral activity against DTMUV. These results indicated that duTYK2 played a critical role in duck antiviral innate immunity.

Keywords: Duck; Innate immunity; TYK2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antiviral Agents / metabolism
  • Avian Proteins / chemistry
  • Avian Proteins / genetics
  • Avian Proteins / metabolism*
  • Bird Diseases / immunology
  • Bird Diseases / virology
  • Cell Line
  • Cloning, Molecular
  • Cytoplasm / metabolism
  • Ducks / immunology*
  • Ducks / virology
  • Flavivirus / immunology
  • Gene Expression Regulation
  • Immunity, Innate
  • Interferons / metabolism
  • Phylogeny
  • Promoter Regions, Genetic
  • Sequence Alignment
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • TYK2 Kinase / chemistry
  • TYK2 Kinase / genetics
  • TYK2 Kinase / metabolism*
  • Tissue Distribution

Substances

  • Antiviral Agents
  • Avian Proteins
  • Interferons
  • TYK2 Kinase

Supplementary concepts

  • Tembusu virus