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. 2023 Jul 20;15(7):1586.
doi: 10.3390/v15071586.

Astragaloside IV Regulates cGAS-STING Signaling Pathway to Alleviate Immunosuppression Caused by PRRSV Infection

Ke Song  1 , Jia-Ying Yu  1 , Jiang Li  1 , Miao Li  1 , Lu-Yuan Peng  1 , Peng-Fei Yi  1
Affiliations

Astragaloside IV Regulates cGAS-STING Signaling Pathway to Alleviate Immunosuppression Caused by PRRSV Infection

Ke Song et al. Viruses. .

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a global threat to pig health and results in significant economic losses. Impaired innate and adaptive immune responses are evident during PRRSV infection. Cyclic GMP-AMP synthase (cGAS), a classical pattern recognition receptor recognizing mainly intracytoplasmic DNA, induces type I IFN responses through the cGAS-STING signaling pathway. It has also been demonstrated that cGAS-STING is involved in PRRSV infection. This study utilized the qRT-PCR, ELISA, and WB methods to examine the effects of Astragaloside IV (AS-IV) on the regulation of innate immune function and cGAS-STING signaling pathway in porcine alveolar macrophages. The results showed that AS-IV attenuated the decreased innate immune function caused by PRRSV infection, restored the inhibited cGAS-STING signaling pathway, and increased the expression of interferon, ultimately exerting antiviral effects. Moreover, these results suggest that AS-IV may be a promising candidate for a new anti-PRRSV antiviral, and its mechanism of action may provide insights for developing novel antiviral agents.

Keywords: AS-IV; PRRSV; antiviral activity; cGAS-STING; immunosuppression.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The cytotoxic effect of AS-IV on PAM cells was detected by CCK8 method.
Figure 2
Figure 2
Effect of AS-IV antiviral: (A) PRRSV load; (B) N protein expression; (C) Western blot; (D) IFN-β secretion. Data are presented as mean ± SD. ## p < 0.01, vs. the control. ** p < 0.01, vs. the virus group.
Figure 3
Figure 3
Innate immune function of PAM cells after infection with PRRSV: (A) SLA-I secretion; (B) SLA-Ⅱ secretion; (C) CD86 secretion. (D) CD80 secretion. (E) Nramp secretion. (F) SP-A secretion. Data are presented as mean ± SD. ## p < 0.01, vs. the control. ** p < 0.01, * p < 0.01, vs. the virus group.
Figure 4
Figure 4
Relative changes in mRNA expression of innate immune function: (A) SLA-I mRNA expression. (B) SLA-DRB1 mRNA expression. (C) CD86 mRNA expression. (D) CD80 mRNA expression. (E) Nramp mRNA expression. (F) SP-A mRNA expression. Data are presented as mean ± SD. ## p < 0.01, vs. the control. ** p < 0.01, vs. the virus group.
Figure 5
Figure 5
Relative changes in mRNA expression of c GAS-STING signal pathway: (A) cGAS mRNA expression. (B) TBK1 mRNA expression. (C) IRF-3 mRNA expression. (D) STING mRNA expression. (E) IFN-β mRNA expression. (F) OAS1 mRNA expression. (G) ISG15 mRNA expression. (H) cGAMP secretion. Data are presented as mean ± SD. ## p < 0.01, vs. the control. ** p < 0.01, * p < 0.01, vs. the virus group.
Figure 6
Figure 6
AS-IV regulates relative changes in protein expression of cGAS-STING signal pathway: (A) western blotting analysis of protein expression. (B) cGAS protein expression. (C) TBK1 protein expression. (D) IRF-3 protein expression. (E) IFN-β protein expression. (F) STING protein expression. Data are presented as mean ± SD. ## p < 0.01, vs. the control. ** p < 0.01, vs. the virus group.
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