Vagal-mAChR4 signaling promotes Friend virus complex (FV)-induced acute erythroleukemia

Shuting Song; Zhekai Lin; Caiqi Zhao; Jing Wen; Jie Chen; Shitao Xie; Huaxin Qi; Jianhua Wang; Xiao Su

doi:10.1016/j.virs.2023.05.005

June 2023

Citation: Shuting Song, Zhekai Lin, Caiqi Zhao, Jing Wen, Jie Chen, Shitao Xie, Huaxin Qi, Jianhua Wang, Xiao Su. Vagal-mAChR4 signaling promotes Friend virus complex (FV)-induced acute erythroleukemia .VIROLOGICA SINICA, 2023, 38(3) : 429-439. http://dx.doi.org/10.1016/j.virs.2023.05.005

Vagal-mAChR4 signaling promotes Friend virus complex (FV)-induced acute erythroleukemia

Shuting Song ^a,b,c ,
Zhekai Lin ^a,b,c ,
Caiqi Zhao ^a,b,c ,
Jing Wen ^a,b,c ,
Jie Chen ^a,b,c ,
Shitao Xie ^a,b,c ,
Huaxin Qi ^a,b,c ,
Jianhua Wang ^d ,
Xiao Su ^{a,b,c,e
,,}

a. Unit of Respiratory Infection and Immunity, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China;
b. CAS Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China;
c. University of Chinese Academy of Sciences, Beijing, 101408, China;
d. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China;
e. Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai, 200031, China

Corresponding author: Xiao Su, xsu@ips.ac.cn
Received Date: 04 July 2022
Accepted Date: 08 May 2023
Available online: 10 May 2023

Abstract

Erythroleukemia belongs to acute myeloid leukemia (AML) type 6 (M6), and treatment remains difficult due to the poor prognosis of the disease. Friend virus (FV) is a complex of two viruses: Friend murine leukemia virus (F-MuLV) strain along with a defective spleen focus-forming virus (SFFV), which can induce acute erythroleukemia in mice. We have previously reported that activation of vagal α7 nicotinic acetylcholine receptor (nAChR) signaling promotes HIV-1 transcription. Whether vagal muscarinic signaling mediates FV-induced erythroleukemia and the underlying mechanisms remain unclear. In this study, sham and vagotomized mice were intraperitoneally injected with FV. FV infection caused anemia in sham mice, and vagotomy reversed this change. FV infection increased erythroblasts ProE, EryA, and EryB cells in the spleen, and these changes were blocked by vagotomy. In bone marrow, FV infection reduced EryC cells in sham mice, an effect that was counteracted by vagotomy. FV infection increased choline acetyltransferase (ChAT) expression in splenic CD4⁺ and CD8⁺ T cells, and this change was reversed by vagotomy. Furthermore, the increase of EryA and EryB cells in spleen of FV-infected wild-type mice was reversed after deletion of ChAT in CD4⁺ T cells. In bone marrow, FV infection reduced EryB and EryC cells in sham mice, whereas lack of ChAT in CD4⁺ T cells did not affect this change. Activation of muscarinic acetylcholine receptor 4 (mAChR4) by clozapine N-oxide (CNO) significantly increased EryB in the spleen but decreased the EryC cell population in the bone marrow of FV-infected mice. Thus, vagal-mAChR4 signaling in the spleen and bone marrow synergistically promotes the pathogenesis of acute erythroleukemia. We uncover an unrecognized mechanism of neuromodulation in erythroleukemia.
- Vagus nerve
- , Friend virus (FV)
- , Acute erythroleukemia
- , Erythroblast
- , Choline acetyltransferase (ChAT)

Electronic Supplementary Material

10.1016j.virs.2023.05.005-ESM.docx
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