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

Singh M, Brahma B, Maharana J, Patra MC, Kumar S, Mishra P, Saini M, De BC, Mahanty S, Datta TK, De S - PLoS ONE (2014)

Bottom Line: Moreover, binding free energy calculation revealed that MDA5 had a greater affinity towards dsRNA compared to RIG1.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.

View Article: PubMed Central - PubMed

Affiliation: Animal Genomics Lab, Animal Biotechnology Center, National Dairy Research Institute, Karnal, Haryana, India.

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.

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Poly I:C induced expression levels of RLR genes in buffalo foetal fibroblast cells over different time intervals.Relative fold change in mRNA of (A) RIG1 (B) MDA5 and (C) LGP2 over control has been shown.
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pone-0089788-g005: Poly I:C induced expression levels of RLR genes in buffalo foetal fibroblast cells over different time intervals.Relative fold change in mRNA of (A) RIG1 (B) MDA5 and (C) LGP2 over control has been shown.

Mentions: As shown in Figure 5, RLR genes showed no change in expression after 1 h post treatment, but RIG1 and MDA5 genes were up-regulated (p<0.01) after 4 h post treatment. Maximum expression of these genes was seen during 6 h post treatment. Afterwards, the expression of RIG1 was sustained at a higher level until 48 h. The level of MDA5 dropped transiently during 12 h, but increased again during subsequent intervals of experiment. The expression pattern of LGP2 followed a slightly different pattern (Figure 5C). The mRNA expression level of LGP2 was significantly higher (p<0.01) during 6 h and was maximum at 24 h after poly I:C treatment. It appeared that the amplitude of response was higher for MDA5, while RIG1 maintained a sustained response following poly I:C treatment.


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

Singh M, Brahma B, Maharana J, Patra MC, Kumar S, Mishra P, Saini M, De BC, Mahanty S, Datta TK, De S - PLoS ONE (2014)

Poly I:C induced expression levels of RLR genes in buffalo foetal fibroblast cells over different time intervals.Relative fold change in mRNA of (A) RIG1 (B) MDA5 and (C) LGP2 over control has been shown.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3935933&req=5

pone-0089788-g005: Poly I:C induced expression levels of RLR genes in buffalo foetal fibroblast cells over different time intervals.Relative fold change in mRNA of (A) RIG1 (B) MDA5 and (C) LGP2 over control has been shown.
Mentions: As shown in Figure 5, RLR genes showed no change in expression after 1 h post treatment, but RIG1 and MDA5 genes were up-regulated (p<0.01) after 4 h post treatment. Maximum expression of these genes was seen during 6 h post treatment. Afterwards, the expression of RIG1 was sustained at a higher level until 48 h. The level of MDA5 dropped transiently during 12 h, but increased again during subsequent intervals of experiment. The expression pattern of LGP2 followed a slightly different pattern (Figure 5C). The mRNA expression level of LGP2 was significantly higher (p<0.01) during 6 h and was maximum at 24 h after poly I:C treatment. It appeared that the amplitude of response was higher for MDA5, while RIG1 maintained a sustained response following poly I:C treatment.

Bottom Line: Moreover, binding free energy calculation revealed that MDA5 had a greater affinity towards dsRNA compared to RIG1.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.

View Article: PubMed Central - PubMed

Affiliation: Animal Genomics Lab, Animal Biotechnology Center, National Dairy Research Institute, Karnal, Haryana, India.

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.

Show MeSH