Interferon Regulatory Factor 3-Mediated Signaling Limits Middle-East Respiratory Syndrome (MERS) Coronavirus

Arinjay Banerjee1, Darryl Falzarano2,3, Noreen Rapin4

  • 1Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada. banera9@mcmaster.ca.

Viruses
|February 21, 2019
PubMed

Insights

Insectivorous bats may host Middle-East respiratory syndrome coronavirus (MERS-CoV). Bat cells resist MERS-CoV by maintaining antiviral interferon beta (IFNβ) responses, unlike human cells.

Area of Science:

  • Virology
  • Immunology
  • Bat Biology

Background:

  • Insectivorous bats are suspected ancestral hosts of MERS-CoV.
  • MERS-CoV has a high fatality rate in humans (35%) and counteracts human antiviral responses.
  • Bats infected with MERS-CoV show no disease signs, suggesting bats possess effective antiviral mechanisms.

Purpose of the Study:

  • To test if MERS-CoV replicates less efficiently in bat cells due to an inability to subvert bat antiviral responses.
  • To investigate the role of interferon beta (IFNβ) and IRF3 in bat antiviral immunity against MERS-CoV.

Main Methods:

  • Infection of human and bat (Eptesicus fuscus) cells with MERS-CoV.
  • Measurement of viral titers and IFNβ response.
  • Analysis of IRF3 activation in response to poly(I:C) (a viral RNA mimic).
  • IRF3 knockdown using small-interfering RNA (siRNA).

Main Results:

  • MERS-CoV replicated to higher titers in human cells compared to bat cells.
  • MERS-CoV suppressed IFNβ response in human cells but not in bat cells.
  • Bat IRF3 activation (nuclear translocation, post-translational modifications) was observed upon poly(I:C) stimulation.
  • IRF3 was essential for IFNβ induction in bat cells against MERS-CoV and poly(I:C).

Conclusions:

  • Bat innate antiviral signaling, specifically the IRF3-IFNβ pathway, is resistant to MERS-CoV-mediated suppression.
  • Eptesicus fuscus bat cells exhibit robust antiviral responses against MERS-CoV, contributing to their asymptomatic infection.
  • Understanding these bat antiviral mechanisms could inform strategies against MERS-CoV in humans.

Related Concept Videos

Transcription Factors02:16

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.7K
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
11.8K
Limiting Reactant02:27

Limiting Reactant

The relative amounts of reactants and products represented in a balanced chemical equation are often referred to as stoichiometric amounts. However, in reality, the reactants are not always present in the stoichiometric amounts indicated by the balanced equation.
69.9K
What is Cell Signaling?02:03

What is Cell Signaling?

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
130.3K
Cell-surface Signaling01:21

Cell-surface Signaling

Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
54.3K
The Number e as a Limit01:29

The Number e as a Limit

The number e is a fundamental constant in calculus, playing a central role in describing continuous change, particularly exponential growth. It is most naturally defined through its relationship with the natural logarithm, which is the inverse of the exponential function with base e. This relationship allows e to be characterized using basic principles of differentiation rather than as an arbitrary numerical constant.A key property of the natural logarithm function, ln x, is that its derivative...
82