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Ligand-of-Numb protein X1 controls the coxsackievirus B3-induced myocarditis via regulating the stability of coxsackievirus and adenovirus receptor

Genes & Immunity volume 23, pages 42–46 (2022)Cite this article

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Abstract

Group B coxsackieviruses (CVBs) are the main cause of virus-induced myocarditis. CVBs use coxsackievirus and adenovirus receptor (CAR) for infection and targeting CAR has been shown to ameliorate CVBs-induced myocarditis. Ligand-of-Numb protein X1 (LNX1) is an E3 ubiquitin ligase that was shown to interact with CAR. However, the precise effect of LNX1 on CAR and the roles of LNX1 on CVBs-induced myocarditis remain unknown. In the present study, we generated mice deficient in LNX1 in the heart and evaluated the symptoms of myocarditis after CVB3 infection. We also monitored the expression and ubiquitination of CAR in LNX1-deficient cardiomyocytes after CVBs infection. We found that CVBs infection decreased CAR expression while promoted the expression of LNX1. Mice with deficiency of LNX1 in the heart had normal myocardial development while had deteriorated myocarditis symptoms after CVB3 infection. In LNX1-deficient cardiomyocytes, decreased ubiquitination of CAR and upregulation of CAR were observed after CVB3 infection. In summary, LNX1 controls CVB3-induced myocarditis by regulating the expression of CAR.

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Fig. 1: Coxsackievirus B3 infection induced the expression of LNX1, but inhibited CAR expression.
Fig. 2: The deficiency of LNX1 did not affect heart development.
Fig. 3: The lack of LNX1 in cardiomyocytes deteriorated the symptoms of CVB3-induced myocarditis.
Fig. 4: LNX1 deficiency suppressed the ubiquitination and degradation of CAR.

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Authors and Affiliations

  1. Department of Cardiology, XI’AN International Medical Center Hospital, No. 777, Xitai Road, Chang’an District, Xi’an, 710100, Shaanxi, China

    Ting Zhang, Changying Wang, Jinjuan Wei, Zhenyin Zhu, Xiaoni Wang & Chuang Sun

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  1. Ting Zhang
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  2. Changying Wang
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  3. Jinjuan Wei
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  4. Zhenyin Zhu
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Contributions

TZ, CW, JW, ZZ, XW, and CS did the experiments, analyzed the data, wrote the paper; CS supervised the study; TZ and CS conceived the study.

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Correspondence to Chuang Sun.

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Zhang, T., Wang, C., Wei, J. et al. Ligand-of-Numb protein X1 controls the coxsackievirus B3-induced myocarditis via regulating the stability of coxsackievirus and adenovirus receptor. Genes Immun 23, 42–46 (2022). https://doi.org/10.1038/s41435-022-00163-x

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