Insight into buffalo (Bubalus bubalis) RIG1 and MDA5 receptors: a comparative study on dsRNA recognition and in-vitro antiviral response

PLoS One. 2014 Feb 26;9(2):e89788. doi: 10.1371/journal.pone.0089788. eCollection 2014.

Abstract

RIG1 and MDA5 have emerged as important intracellular innate pattern recognition receptors that recognize viral RNA and mediate cellular signals controlling Type I interferon (IFN-I) response. Buffalo RIG1 and MDA5 genes were investigated to understand the mechanism of receptor induced antiviral response. Sequence analysis revealed that RIG1 and MDA5 maintain a domain arrangement that is common in mammals. Critical binding site residues of the receptors are evolutionary conserved among mammals. Molecular dynamics simulations suggested that RIG1 and MDA5 follow a similar, if not identical, dsRNA binding pattern that has been previously reported in human. Moreover, binding free energy calculation revealed that MDA5 had a greater affinity towards dsRNA compared to RIG1. Constitutive expressions of RLR genes were ubiquitous in different tissues without being specific to immune organs. Poly I:C stimulation induced elevated expressions of IFN-β and IFN-stimulated genes (ISGs) through interferon regulatory factors (IRFs) mediated pathway in buffalo foetal fibroblast cells. The present study provides crucial insights into the structure and function of RIG1 and MDA5 receptors in buffalo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Analysis of Variance
  • Animals
  • Base Sequence
  • Buffaloes / immunology*
  • Buffaloes / metabolism
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • DNA Primers / genetics
  • Immunohistochemistry
  • Interferon Type I / metabolism
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Phylogeny
  • Poly I-C
  • RNA, Double-Stranded / metabolism*
  • RNA, Viral / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Receptors, Pattern Recognition / metabolism*
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism*
  • Sequence Analysis, DNA
  • Signal Transduction / immunology*

Substances

  • DNA Primers
  • Interferon Type I
  • RNA, Double-Stranded
  • RNA, Viral
  • Receptors, Pattern Recognition
  • Receptors, Retinoic Acid
  • DEAD-box RNA Helicases
  • Poly I-C

Grants and funding

The study was supported by a grant (BT/PR3111/AAQ/1/474/2011) received from Department of Biotechnology (DBT), Ministry of Science and Technology, Govt. of India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.