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Reducing lipid peroxidation attenuates stress-induced susceptibility to herpes simplex virus type 1

   
@article{APS10891,
	author = {Jing-yu Weng and Xin-xing Chen and Xiao-hua Wang and Hui-er Ye and Yan-ping Wu and Wan-yang Sun and Lei Liang and Wen-jun Duan and Hiroshi Kurihara and Feng Huang and Xin-xin Sun and Shu-hua Ou-Yang and Rong-rong He and Yi-fang Li},
	title = {Reducing lipid peroxidation attenuates stress-induced susceptibility to herpes simplex virus type 1},
	journal = {Acta Pharmacologica Sinica},
	volume = {44},
	number = {9},
	year = {2023},
	keywords = {},
	abstract = {Psychological stress increases the susceptibility to herpes simplex virus type 1 (HSV-1) infection. There is no effective intervention due to the unknown pathogenesis mechanisms. In this study we explored the molecular mechanisms underlying stress-induced HSV-1 susceptibility and the antiviral effect of a natural compound rosmarinic acid (RA) in vivo and in vitro. Mice were administered RA (11.7, 23.4 mg·kg−1·d−1, i.g.) or acyclovir (ACV, 206 mg·kg−1·d−1, i.g.) for 23 days. The mice were subjected to restraint stress for 7 days followed by intranasal infection with HSV-1 on D7. At the end of RA or ACV treatment, mouse plasma samples and brain tissues were collected for analysis. We showed that both RA and ACV treatment significantly decreased stress-augmented mortality and alleviated eye swelling and neurological symptoms in HSV-1-infected mice. In SH-SY5Y cells and PC12 cells exposed to the stress hormone corticosterone (CORT) plus HSV-1, RA (100 μM) significantly increased the cell viability, and inhibited CORT-induced elevation in the expression of viral proteins and genes. We demonstrated that CORT (50 μM) triggered lipoxygenase 15 (ALOX15)-mediated redox imbalance in the neuronal cells, increasing the level of 4-HNE-conjugated STING, which impaired STING translocation from the endoplasmic reticulum to Golgi; the abnormality of STING-mediated innate immunity led to HSV-1 susceptibility. We revealed that RA was an inhibitor of lipid peroxidation by directly targeting ALOX15, thus RA could rescue stress-weakened neuronal innate immune response, thereby reducing HSV-1 susceptibility in vivo and in vitro. This study illustrates the critical role of lipid peroxidation in stress-induced HSV-1 susceptibility and reveals the potential for developing RA as an effective intervention in anti-HSV-1 therapy.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/10891}
}