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

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

机构地区：[1]Unit of Respiratory Infection and Immunity,Institute Pasteur of Shanghai,Chinese Academy of Sciences,Shanghai,200031,China [2]CAS Key Laboratory of Molecular Virology and Immunology,Institute Pasteur of Shanghai,Chinese Academy of Sciences,Shanghai,200031,China [3]University of Chinese Academy of Sciences,Beijing,101408,China [4]Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou,510530,China [5]Shanghai Key Laboratory of Lung Inflammation and Injury,Shanghai,200031,China

出　　处：《Virologica Sinica》2023年第3期429-439,共11页中国病毒学（英文版）

基　　金：from National Natural Science Foundation of China(82241042,81970075,81730001,91942305);National Key Research and Development Program of China(2022YFC2304700);Science and Technology Commission of Shanghai Municipality(20DZ2261200);Innovative research team of high-level local universities in Shanghai(SHSMU-ZDCX20210602).

摘　　要：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 eryth-roleukemia in mice.We have previously reported that activation of vagalα7 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 coun-teracted by vagotomy.FV infection increased choline acetyltransferase(ChAT)expression in splenic CD4^(+)and CD8þT 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.

关 键 词：Vagus nerve Friend virus(FV) Acute erythroleukemia ERYTHROBLAST Choline acetyltransferase(ChAT) 

分 类 号：R373.31[医药卫生—病原生物学]