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. 2023 Oct 29;15(11):2172.
doi: 10.3390/v15112172.

Naringenin Improves Innate Immune Suppression after PRRSV Infection by Reactivating the RIG-I-MAVS Signaling Pathway, Promoting the Production of IFN-I

Jiaying Yu  1 , Haitao Shi  1 , Ke Song  1 , Yuxin Yang  1 , Xinmiao Li  1 , Luyuan Peng  1 , Bendong Fu  1 , Pengfei Yi  1
Affiliations

Naringenin Improves Innate Immune Suppression after PRRSV Infection by Reactivating the RIG-I-MAVS Signaling Pathway, Promoting the Production of IFN-I

Jiaying Yu et al. Viruses. .

Abstract

Porcine reproductive and respiratory syndrome (PRRS) has been prevalent for nearly forty years since it was first reported. It has been one of the major diseases jeopardizing the healthy development of the world swine industry, as well as causing great economic losses to the industry's economic development. Furthermore, no way has been found to combat the disease due to the immunosuppressive properties of its pathogen porcine reproductive and respiratory syndrome virus (PRRSV) infection. We previously examined the mRNA expression of IFN-I in PRRSV-infected Marc-145 cells at different time periods using qRT-PCR, and found that the mRNA expression of IFN-I in the late stage of PRRSV infection showed suppression. Naringenin is a flavonoid found in citrus fruits and has a very wide range of pharmacological activities. Therefore, the aim of the present study was to investigate the modulatory effect of naringenin on the suppressed innate immune response after PRRSV infection. The expression of IFN-I, IL-10, and ISGs in the late stage of PRRSV infection was examined using qRT-PCR, and the results showed that naringenin improved the expression of antiviral cytokines suppressed by PRRSV infection. Further results showed that naringenin treatment significantly up-regulated the expression of proteins related to the RIG-I-MAV immune signaling pathway, and that naringenin could not significantly activate the RIG-I-MAVS signaling pathway after the addition of the RIG-I inhibitor Cyclo. Overall, these data demonstrated that naringenin could improve the innate immune response suppressed by PRRSV infection by modulating the RIG-I-MAVS signaling pathway. Therefore, our study will provide a theoretical basis for the development of naringenin as a drug against immunosuppressive viral infectious disease infections.

Keywords: PRRSV; RIG-I-MAVS; innate immune suppression; naringenin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The maximum safe concentration range of naringenin on Marc-145 was detected using the CCK8 method. *** p < 0.001, vs. the control group.
Figure 2
Figure 2
PRRSV infection with mRNA expression of IFN-I at different time periods. (A) IFN-α mRNA expression; (B) IFN-β mRNA expression. Data are expressed as the mean and SD of three independent experiments.
Figure 3
Figure 3
Naringenin up-regulates the expression of immune cytokines. (A) IFN-α mRNA expression; (B) IFN-β mRNA expression; (C) IL-10 mRNA expression; (D) TNF-α mRNA expression; (E) IL-1β mRNA expression; (F) IL-6 mRNA expression; (G) cxcl-8 mRNA expression. Data are expressed as the mean and SD of three independent experiments. ** p < 0.01, * p < 0.05, vs. the virus group. ## p < 0.01, vs. the control group.
Figure 4
Figure 4
Naringenin up-regulates the expression of ISGs. (A) CH25H mRNA expression; (B) MOV10 mRNA expression; (C) OAS1 mRNA expression; (D) OASL mRNA expression; (E) ISG15 mRNA expression; (F) IFIT1 mRNA expression; (G) IFITM1 mRNA expression; (H) TRIM25 mRNA expression; (I) GBP1 mRNA expression; (J) RASD2 mRNA expression. Data are expressed as the mean and SD of three independent experiments. *** p < 0.001, ** p < 0.01, * p < 0.05, vs. the control group. ### p < 0.001, ## p < 0.01, # p < 0.05, vs. the virus group.
Figure 5
Figure 5
Naringenin up-regulates the expression of genes and proteins related to the RIG-I-MAVS signaling pathway. (A) RIG-I mRNA expression; (B) MAVS mRNA expression; (C) TBK1 mRNA expression; (D) IRF3 mRNA expression. Data are expressed as the mean and SD of three independent experiments. *** p < 0.001, ** p < 0.01, vs. the control group. ### p < 0.001, # p < 0.05, vs. the virus group.
Figure 6
Figure 6
Naringenin up-regulates the expression of genes and proteins related to the RIG-I-MAVS signaling pathway. (A) Western blotting analysis of protein expression; (B) RIG-I protein expression; (C) MAVS protein expression; (D) TBK1 protein expression; (E) p-IRF3 protein expression. Data are expressed as the mean and SD of three independent experiments. * p < 0.05, vs. the control group. ### p < 0.001, ## p < 0.01, # p < 0.05, vs. the virus group.
Figure 7
Figure 7
Naringenin exerts innate immunomodulatory effects by modulating the RIG-I-MAVS signaling pathway. (A) Western blotting analysis of protein expression; (B) RIG-I protein expression; (C) MAVS protein expression; (D) TBK1 protein expression; (E) p-IRF3 protein expression. Data are expressed as the mean SD of three independent experiments. *** p < 0.001, vs. the control group. ### p < 0.001, vs. the virus group.
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