4.6 Article

Molecular cloning and functional characterization of porcine DNA-dependent activator of IFN-regulatory factors (DAI)

Journal

DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
Volume 34, Issue 3, Pages 293-299

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.dci.2009.10.007

Keywords

Porcine; DAI; Type I interferon; Innate immunity

Funding

  1. National Key Technology R&D Programme of China [2007BAD86BO6, 2006BAD06AO4]
  2. National Basic Research Program (973) [2005CB523200]
  3. New Century Excellent Talent Project [NCET-07-0347]
  4. National Natural Sciences Foundation of China [30871871, 30972189]

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The DNA-dependent activator of IFN-regulatory factors (DAI) is a recently identified DNA sensor for intracellular DNA that triggers a signal for the production of type I IFN. Here we report the cloning and characterization of porcine DAI (poDAI). The full-length of poDAI encodes 439 amino acids, contains two N-terminal DNA-binding domains and shows similarity to mouse, rat, dog, monkey, human, horse and cattle counterparts ranging from 44% to 67%. poDAI mRNA expression was mainly detected in spleen, lung, kidney and small intestine. Over-expression of poDAI activated transcription factors IRF3 and NF-kappa B and induced IFN-beta in different porcine cell lines, but to varying degrees. Deletion mutant analysis revealed that both the DNA-binding domains and the C-terminus are required for full activation of IFN-beta. siRNA targeting poDAI significantly decreased poly(dAT:dAT)- or Pseudorabies virus (PRV)-induced IFN-beta activation. These results indicate that DAI is an important immuno-regulator of the porcine innate immune system. (C) 2009 Elsevier Ltd. All rights reserved.

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