June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
IFIT3/P60 Expression Reflects Cell Specific Response to Viral Infection
Author Affiliations & Notes
  • Nathaniel Sears
    Cleveland Clinic, Cole Eye Institute, Cleveland, OH
  • Steffen Christoffersen
    Cleveland Clinic, Cole Eye Institute, Cleveland, OH
  • George Hoppe
    Cleveland Clinic, Cole Eye Institute, Cleveland, OH
  • Jonathan E Sears
    Cleveland Clinic, Cole Eye Institute, Cleveland, OH
  • Footnotes
    Commercial Relationships Nathaniel Sears, None; Steffen Christoffersen, None; George Hoppe, None; Jonathan Sears, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 838. doi:
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      Nathaniel Sears, Steffen Christoffersen, George Hoppe, Jonathan E Sears; IFIT3/P60 Expression Reflects Cell Specific Response to Viral Infection. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):838.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Extracellular RNA viruses are recognized by Toll-like receptor 3, and when intracellular by retinoic acid inducible gene I (RIG-I)/MDA5 receptors, stimulating formation of the mitochondrial antiviral signaling complex that leads to NFkB and interferon response factor 3 (IRF3) activation. The cell phenotype then has a divergent response that can include either programmed cell death or chronic inflammation. The purpose of this study is to determine how cells regulate their fate between these two phenotypes by analyzing IRF-3 dependent genes.

Methods: Cultured ARPE-19 cells and human Muller cells were challenged with dsRNA. Immunoanalysis of IRF-3, pIRF3, caspase-8, and interferon-induced proteins with tetratricopeptide repeats (IFIT3/P60) were performed.

Results: Both Muller cells and ARPE-19 cells demonstrate similar induction of IRF3 and pIRF3 expression in response to dsRNA. Caspase 8 levels were similar between these cells as well. These levels were identical when normalized to actin, and demonstrated a similar kinetics when measured at 0,8,24, and 48 hours. However, IFIT3/P60 was robustly expressed in ARPE-19 cells in comparison to Muller cells and exhibited markedly different kinetics. ARPE IFIT3 levels rapidly peaked at 24 hours and became attenuated at 48 hours, whereas Muller cell IFIT3 protein peaked at 8 hours and sustained this level at 48 hours.

Conclusions: Both Muller cells and ARPE-19 demonstrate cell specific responses to extracellular virus manifested by differential IFIT3 induction. This finding may reflect an IRF3 independent pathway. Differential responses to identical dsRNA stimulus is therefore cell specific and demonstrates the feasibility of using this approach to further understand the molecular mechanism that underlies regulation between chronic inflammation and programmed cell death.


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