Investigating TIP30-Mediated regulation of mTORC1 signaling as a therapeutic strategy for coxsackievirus B3-Induced viral myocarditis.

Autor: Liu XL; Cardiovascular Medicine, Xinxiang Central Hospital, Xinxiang, 453000, Henan, China., Hou YY; Cardiovascular Medicine, Xinxiang Central Hospital, Xinxiang, 453000, Henan, China., Su SH; Cardiovascular Medicine, Xinxiang Central Hospital, Xinxiang, 453000, Henan, China., Wu X; Cardiovascular Medicine, Xinxiang Central Hospital, Xinxiang, 453000, Henan, China., Wang ZF; Cardiovascular Medicine, Xinxiang Central Hospital, Xinxiang, 453000, Henan, China. Electronic address: wangzhifang1964@163.com.
Jazyk: angličtina
Zdroj: Virology [Virology] 2024 Sep; Vol. 597, pp. 110156. Date of Electronic Publication: 2024 Jun 21.
DOI: 10.1016/j.virol.2024.110156
Abstrakt: This study aims to elucidate the role of TIP30 (30 KDa HIV-1 TAT-Interacting Protein) in the progression of coxsackievirus B3 (CVB3)-induced viral myocarditis. TIP30 knockout and wildtype mice were intraperitoneally infected with CVB3 and evaluated at day 7 post-infection. HeLa cells were transfected with TIP30 lentiviral particles and subsequently infected with CVB3 to evaluate viral replication, cellular pathogenesis, and mechanistic target of rapamycin complex 1 (mTORC1) signaling. Deletion of the TIP30 gene heightened heart virus titers and mortality rates in mice with CVB3-induced myocarditis, exacerbating cardiac damage and fibrosis, and elevating pro-inflammatory factors level. In vitro experiments demonstrated the modulation of mTORC1 signaling by TIP30 during CVB3 infection in HeLa cells. TIP30 overexpression mitigated CVB3-induced cellular pathogenesis and VP1 expression, with rapamycin, an mTOR1 inhibitor, reversing these effects. These findings suggest TIP30 plays a critical protective role against CVB3-induced myocarditis by regulating mTORC1 signaling.
Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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