IDO1 promotes CSFV replication by mediating tryptophan metabolism to inhibit NF-κB signaling.

Autor:	Zhao F; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Huang Y; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Ji J; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Liu X; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Li X; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Zou L; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Wu K; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Liu Xd; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Zeng S; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Wang X; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Hu W; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Song Y; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Lu Z; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Zhou B; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Li P; Wen's Foodstuffs Group Co., Ltd., Xinxing, China, Yunfu, China., Wang W; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Zhao M; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Chen J; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Yi L; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China., Fan S; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, China.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2024 Jul 23; Vol. 98 (7), pp. e0045824. Date of Electronic Publication: 2024 May 30.
DOI:	10.1128/jvi.00458-24
Abstrakt:	Tryptophan metabolism plays a crucial role in facilitating various cellular processes essential for maintaining normal cellular function. Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the conversion of tryptophan (Trp) into kynurenine (Kyn), thereby initiating the degradation of Trp. The resulting Kyn metabolites have been implicated in the modulation of immune responses. Currently, the role of IDO1-mediated tryptophan metabolism in the process of viral infection remains relatively unknown. In this study, we discovered that classical swine fever virus (CSFV) infection of PK-15 cells can induce the expression of IDO1, thereby promoting tryptophan metabolism. IDO1 can negatively regulate the NF-κB signaling by mediating tryptophan metabolism, thereby facilitating CSFV replication. We found that silencing the IDO1 gene enhances the expression of IFN-α, IFN-β, and IL-6 by activating the NF-κB signaling pathway. Furthermore, our observations indicate that both silencing the IDO1 gene and administering exogenous tryptophan can inhibit CSFV replication by counteracting the cellular autophagy induced by Rapamycin. This study reveals a novel mechanism of IDO1-mediated tryptophan metabolism in CSFV infection, providing new insights and a theoretical basis for the treatment and control of CSFV.IMPORTANCEIt is well known that due to the widespread use of vaccines, the prevalence of classical swine fever (CSF) is shifting towards atypical and invisible infections. CSF can disrupt host metabolism, leading to persistent immune suppression in the host and causing significant harm when co-infected with other diseases. Changes in the host's metabolic profiles, such as increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, can also influence virus replication. Mammals utilize various pathways to modulate immune responses through amino acid utilization, including increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, thereby limiting viral replication. Therefore, this study proposes that targeting the modulation of tryptophan metabolism may represent an effective approach to control the progression of CSF. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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