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A bioinformatics based approach to characterize interferon-stimulated gene signatures

Friday, November 08, 2013 — Poster Session IV

2:00 p.m. – 4:00 p.m.

FAES Academic Center (Upper-Level Terrace)

FDA/CBER

IMMUNO-28

Authors

  • TC Theisen
  • LA Renn
  • P Hillyer
  • RL Rabin

Abstract

Type I interferons (IFN) include IFN-beta, IFN-omega, and twelve subtypes of IFN-alpha, and share the heterodimeric receptor comprised of IFNAR1 and IFNAR2. Type III IFNs include IFN-lambda-1, -lambda2, and -lambda3, signal through a heterodimer comprised of IL28RA and IL-10RB, share activation of STAT1/STAT2 and induce expression of many of the same interferon stimulated genes (ISG) as type I IFN. Types I and III IFN, however, trigger additional signaling pathways, and are expressed differentially in response to different TLR ligands and pathogens—both of which suggest unique functional consequences to specific IFN subtypes. To detect unique functional responses to IFN alone or in combination, we first designed a qRT-PCR assay for the 50 plus ISG that are transcription factors, and then employed a bioinformatics approach through local and global nucleotide and peptide alignments with the goal of designing degenerate primers for regions of sequence similarity among more than 500 ISG. We predict that together these approaches will provide both a screen for detecting novel functional consequences of IFN signaling through a variety of cellular pathways and a tool for deciphering unique roles for IFN subtypes in the innate response to viral pathogens.

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