Related Experiment Video

Updated: Jul 5, 2025

High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
10:00

High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes

Published on: March 24, 2015

13.4K

TNIK regulation of interferon signaling and endothelial cell response to virus infection

Khanh M Chau1, Abishai Dominic1,2, Eleanor L Davis3

  • 1Department of Cardiovascular Sciences, Center for Cardiovascular Sciences, Academic Institute, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, United States.

Frontiers in Cardiovascular Medicine
|January 24, 2024
PubMed
Abstract

Insights

Traf2 and Nck-interacting kinase (TNIK) depletion in endothelial cells inhibits the interferon pathway, impacting viral response. TNIK is crucial for endothelial cell defense against adenovirus infection.

Area of Science:

  • Endothelial cell biology
  • Virology
  • Immunology

Background:

  • Traf2 and Nck-interacting kinase (TNIK) has known roles in cancer but its function in endothelial cells (ECs) is largely unknown.
  • Endothelial cells play critical roles in vascular health and immunity.

Purpose of the Study:

  • To investigate the role of TNIK in endothelial cells.
  • To determine the impact of TNIK depletion on EC responses, particularly to viral infection.

Main Methods:

  • RNA sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) were used to analyze gene expression changes in TNIK-depleted ECs.
  • Quantitative reverse transcription PCR (qRT-PCR), immunoblotting, and ELISA were employed for validation.
  • Adenovirus transduction models were used to assess viral uptake and cytopathic effects.

Main Results:

  • TNIK depletion in ECs resulted in over 450 differentially expressed genes.
  • IPA revealed significant inhibition of the interferon (IFN) pathway and downregulation of IFN-related genes and hypercytokinemia/hyperchemokinemia.
  • TNIK depletion did not affect adenovirus uptake but induced cytopathic effects in response to wild-type adenovirus.

Conclusions:

  • TNIK is a key regulator of the endothelial cell response to viral infections.
  • Modulation of the IFN pathway by TNIK is critical for ECs' antiviral defense mechanisms.
Keywords:
RNA-SeqSTATsTNIKinterferonsvirus infection

More Related Videos

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF311:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

12.0K
Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response12:50

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response

Published on: September 15, 2017

6.6K

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
783
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
2.0K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.1K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.9K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K