RIG-I Has a Role in Immunity Against Haemonchus contortus, a Gastrointestinal Parasite in Ovis aries: A Novel Report

Abstract

Retinoic acid inducible gene I (RIG-I) is associated to the DExD/H box RNA helicases. It is a pattern recognition receptor (PRR), playing a crucial role in the system and is a germ line encoded host sensor to perceive pathogen-associated molecular patterns (PAMPs). So far, reports are available for the role of RIG-I in antiviral immunity. This is the first report in which we have documented the role of RIG-I in parasitic immunity. Haemonchus contortus is a deadly parasite affecting the sheep industry, which has a tremendous economic importance, and the parasite is reported to be prevalent in the hot and humid agroclimatic region. We characterize the RIG-I gene in sheep (Ovis aries) and identify the important domains or binding sites with Haemonchus contortus through in silico studies. Differential mRNA expression analysis reveals upregulation of the RIG-I gene in the abomasum of infected sheep compared with that of healthy sheep, further confirming the findings. Thus, it is evident that, in infected sheep, expression of RIG-I is triggered for binding to more pathogens (Haemonchus contortus). Genetically similar studies with humans and other livestock species were conducted to reveal that sheep may be efficiently using a model organism for studying the role of RIG-I in antiparasitic immunity in humans.

Keywords: Haemonchus contortus; RIG-I; innate immunity; parasite; sheep.

Figure 1

(A) 3-D Structure of RIG-1 gene of sheep. (B) 3-D Structure of RIG-1 gene (surface view) of sheep. (C) RIG-I_C-RD, the C-terminal domain of RIG-I of sheep. (D) RIG-I_C, C-terminal domain of RIG-I protein of sheep.

Figure 2

(A) RLR_C-terminal domain of the gene of sheep. (B) RLR_C_like domain of RIG gene of sheep. (C) LGP2_C, C-terminal domain of Laboratory of Genetics and Physiology 2 (LGP2) of sheep. (D) MDA5_C, C-terminal domain of melanoma differentiation-associated protein 5 of sheep.

Figure 3

(A) MPH1 ERCC4-related helicase (replication, recombination and repair) of sheep. (B) CARD: a protein–protein interaction domain of sheep. (C) PRK13766, Hef nuclease; Provisional.

Figure 4

Protein–protein interaction network of RIG-I gene with associated protein by STRING analysis.

Figure 5

(A–D) Molecular docking of parasitic protein nd₄ with ovine RIG-I, alignment (left) and binding site (right).

Figure 6

(A, B) Molecular docking of parasitic protein 15 kDa secretory protein with ovine RIG-I, alignment (left) and binding site (right). (C,D) Molecular docking of parasitic protein Pgp1 with ovine RIG-I, alignment (left) and binding site (right).

Figure 7

(A, B) Molecular docking of parasitic protein Alpha tubulin with ovine RIG-I, alignment (left) and binding site (right). (C, D) Molecular docking of parasitic protein Glc 5 with ovine RIG-I.

Figure 8

(A) Molecular docking of parasitic protein Beta tubulin with ovine RIG-I, alignment (left) and binding site (right). (B) Molecular docking of parasitic protein Phosphoenol pyruvate carboxy kinase with ovine RIG-I, alignment (left) and binding site (right). (C): Molecular docking of parasitic protein Cystein proteinase with ovine RIG-I, alignment (left) and binding site (right). (D, E) Molecular docking of parasitic protein Galaectin with ovine RIG-I, alignment (left) and binding site (right). (F) Molecular docking of parasitic protein Lectin with ovine RIG-I, alignment (left) and binding site (right).

Figure 9

(A) RIG-I expression profiling for different GALT and lymph node in sheep. (B) RIG-I expression profiling for healthy and Haemonchus contortus–infected sheep from abomasum.

Figure 10

Molecular phylogenetic analysis of sheep with other species based on RIG-I gene.