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RIG-I is required for the inhibition of measles virus by retinoids.

Soye KJ, Trottier C, Richardson CD, Ward BJ, Miller WH - PLoS ONE (2011)

Bottom Line: Vitamin A can significantly decrease measles-associated morbidity and mortality.Retinoid signaling was also found to act in combination with IFN to induce high levels of RIG-I expression.IRF-1 is known to be regulated by retinoids and MeV, but we found recruitment of IRF-1 to the RIG-I promoter by retinoids alone.

View Article: PubMed Central - PubMed

Affiliation: McGill University Health Center Research Institute, Department of Infectious Diseases, McGill University, Montreal, Quebec, Canada.

ABSTRACT
Vitamin A can significantly decrease measles-associated morbidity and mortality. Vitamin A can inhibit the replication of measles virus (MeV) in vitro through an RARα- and type I interferon (IFN)-dependent mechanism. Retinoid-induced gene I (RIG-I) expression is induced by retinoids, activated by MeV RNA and is important for IFN signaling. We hypothesized that RIG-I is central to retinoid-mediated inhibition of MeV in vitro. We demonstrate that RIG-I expression is increased in cells treated with retinoids and infected with MeV. The central role of RIG-I in the retinoid-anti-MeV effect was demonstrated in the Huh-7/7.5 model; the latter cells having non-functional RIG-I. RAR-dependent retinoid signaling was required for the induction of RIG-I by retinoids and MeV. Retinoid signaling was also found to act in combination with IFN to induce high levels of RIG-I expression. RIG-I promoter activation required both retinoids and MeV, as indicated by markers of active chromatin. IRF-1 is known to be regulated by retinoids and MeV, but we found recruitment of IRF-1 to the RIG-I promoter by retinoids alone. Using luciferase expression constructs, we further demonstrated that the IRF-1 response element of RIG-I was required for RIG-I activation by retinoids or IFN. These results reveal that retinoid treatment and MeV infection induces significant RIG-I. RIG-I is required for the retinoid-MeV antiviral response. The induction is dependent on IFN, retinoids and IRF-1.

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Activation of RIG-I promoter only upon combination of MeV infection and retinoid treatment.U937 cells were infected with MeV at an MOI of 0.1 and/or treated with 1 µM ATRA or DMSO for 24 hours. 1000 U/ml of IFNβ was used as a positive control. These samples were then immunoprecipitated the following primary antibodies (A) Acetylate Histone H3 (B) Pol II (C) IRF-1. The pulled-down DNA was analyzed by qPCR using primers specific for the RIG-I promoter as described in the materials and methods. Data presented are representative of experiments performed in triplicate between two and three times (N = 2–3). *p<0.05, **p<0.01, ***p<0.001.
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pone-0022323-g006: Activation of RIG-I promoter only upon combination of MeV infection and retinoid treatment.U937 cells were infected with MeV at an MOI of 0.1 and/or treated with 1 µM ATRA or DMSO for 24 hours. 1000 U/ml of IFNβ was used as a positive control. These samples were then immunoprecipitated the following primary antibodies (A) Acetylate Histone H3 (B) Pol II (C) IRF-1. The pulled-down DNA was analyzed by qPCR using primers specific for the RIG-I promoter as described in the materials and methods. Data presented are representative of experiments performed in triplicate between two and three times (N = 2–3). *p<0.05, **p<0.01, ***p<0.001.

Mentions: To better define the effect of retinoids ± MeV on the transcriptional regulation of RIG-I, chromatin remodeling and the recruitment of proteins associated with transcriptional activation on the RIG-I promoter were investigated in our U937 model. As an indication of chromatin remodeling, acetylation of histone H3 (Figure 6A) and histone H4 (data not shown) was increased following combined ATRA treatment and MeV infection compared to either manipulation alone and significantly increased over control. Further, RNA Polymerase II (Pol II) was strongly recruited to the RIG-I promoter only by IFNβ treatment (positive control) or by the combination of ATRA treatment plus MeV infection (Figure 6B).


RIG-I is required for the inhibition of measles virus by retinoids.

Soye KJ, Trottier C, Richardson CD, Ward BJ, Miller WH - PLoS ONE (2011)

Activation of RIG-I promoter only upon combination of MeV infection and retinoid treatment.U937 cells were infected with MeV at an MOI of 0.1 and/or treated with 1 µM ATRA or DMSO for 24 hours. 1000 U/ml of IFNβ was used as a positive control. These samples were then immunoprecipitated the following primary antibodies (A) Acetylate Histone H3 (B) Pol II (C) IRF-1. The pulled-down DNA was analyzed by qPCR using primers specific for the RIG-I promoter as described in the materials and methods. Data presented are representative of experiments performed in triplicate between two and three times (N = 2–3). *p<0.05, **p<0.01, ***p<0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3139622&req=5

pone-0022323-g006: Activation of RIG-I promoter only upon combination of MeV infection and retinoid treatment.U937 cells were infected with MeV at an MOI of 0.1 and/or treated with 1 µM ATRA or DMSO for 24 hours. 1000 U/ml of IFNβ was used as a positive control. These samples were then immunoprecipitated the following primary antibodies (A) Acetylate Histone H3 (B) Pol II (C) IRF-1. The pulled-down DNA was analyzed by qPCR using primers specific for the RIG-I promoter as described in the materials and methods. Data presented are representative of experiments performed in triplicate between two and three times (N = 2–3). *p<0.05, **p<0.01, ***p<0.001.
Mentions: To better define the effect of retinoids ± MeV on the transcriptional regulation of RIG-I, chromatin remodeling and the recruitment of proteins associated with transcriptional activation on the RIG-I promoter were investigated in our U937 model. As an indication of chromatin remodeling, acetylation of histone H3 (Figure 6A) and histone H4 (data not shown) was increased following combined ATRA treatment and MeV infection compared to either manipulation alone and significantly increased over control. Further, RNA Polymerase II (Pol II) was strongly recruited to the RIG-I promoter only by IFNβ treatment (positive control) or by the combination of ATRA treatment plus MeV infection (Figure 6B).

Bottom Line: Vitamin A can significantly decrease measles-associated morbidity and mortality.Retinoid signaling was also found to act in combination with IFN to induce high levels of RIG-I expression.IRF-1 is known to be regulated by retinoids and MeV, but we found recruitment of IRF-1 to the RIG-I promoter by retinoids alone.

View Article: PubMed Central - PubMed

Affiliation: McGill University Health Center Research Institute, Department of Infectious Diseases, McGill University, Montreal, Quebec, Canada.

ABSTRACT
Vitamin A can significantly decrease measles-associated morbidity and mortality. Vitamin A can inhibit the replication of measles virus (MeV) in vitro through an RARα- and type I interferon (IFN)-dependent mechanism. Retinoid-induced gene I (RIG-I) expression is induced by retinoids, activated by MeV RNA and is important for IFN signaling. We hypothesized that RIG-I is central to retinoid-mediated inhibition of MeV in vitro. We demonstrate that RIG-I expression is increased in cells treated with retinoids and infected with MeV. The central role of RIG-I in the retinoid-anti-MeV effect was demonstrated in the Huh-7/7.5 model; the latter cells having non-functional RIG-I. RAR-dependent retinoid signaling was required for the induction of RIG-I by retinoids and MeV. Retinoid signaling was also found to act in combination with IFN to induce high levels of RIG-I expression. RIG-I promoter activation required both retinoids and MeV, as indicated by markers of active chromatin. IRF-1 is known to be regulated by retinoids and MeV, but we found recruitment of IRF-1 to the RIG-I promoter by retinoids alone. Using luciferase expression constructs, we further demonstrated that the IRF-1 response element of RIG-I was required for RIG-I activation by retinoids or IFN. These results reveal that retinoid treatment and MeV infection induces significant RIG-I. RIG-I is required for the retinoid-MeV antiviral response. The induction is dependent on IFN, retinoids and IRF-1.

Show MeSH
Related in: MedlinePlus