The Mechanism of Antigen-Presentation of Avian Bone Marrowed Dendritic Cells Suppressed by Infectious Bronchitis Virus

Abstract

Coronaviruses are identify in different species of animals, including camels, bats and avian. Avian infectious bronchitis virus (IBV) always infect and invade from the respiratory tract, where submucosal dendritic cells (DCs) are the first guard to defend it. However, different IBV subtypes, such as QX and M41, could suppress the function of dendritic cells and escape the degradation and presentation, which might help coronaviruses to transfer and migrant. Hence, it is necessary to illustrate the uncovered mechanisms how IBV inhibited the antigen-presentation of avian DCs. Initially, we compared two types IBV's function in activating avian bone marrow dendritic cells (BMDCs) and found that both IBV (QX and M41) did not significantly increase the expression of MHCII. Subsequent global analyses identified 21 significantly different expressed (DE) microRNAs and 2888 DE long non-coding RNAs (lncRNAs) in IBV M41 stimulated group, while IBV (QX) stimulation only identified 4 DE microRNAs and 1782 DE lncRNAs. Moreover, GO and KEGG analysis of microRNAs target and lncRNAs lead to endocytosis and cytokine-cytokine receptor interaction, which might contribute to the differences in pathogenicity of QX and M41. Meantime, a significant decrease of the m 6 A modification level in mRNA, but an increased in the ut RNA were observed in avian BMDCs upon the prevalent IBV (QX) infection. Interestingly, an opposite consequence was seen in avian BMDCs during the IBV (M41) infection. Further study found that both non-structural protein 7 (NSP7) and NSP16 inhibited the maturation and cytokines secretion of BMDCs, as well as their antigen-presentation ability. Lastly, we found that gga-miR21, induced and increased by both NSP7 and NSP16, inhibited the antigen presentation of avian BMDCs. Taken together, our results illustrated how IBV inhibited the antigen-presentation of avian DCs and provide a clue for the systemic transmission of the COVID-19.Funding Statement: This work was supported by the National Key Research and Development Program of China (2017YFD500706), the Jiangsu Excellent Youth Natural Science Foundation (BK20190077), the National Natural Science Foundation of China (No. 31702197) to J.L. Moreover, this work was also supported by National Natural Science Foundation of China (31930109 and 31772777), the Fundamental Research Funds for the Central Universities (JCQY201906) and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) to Q.Y and Q.HY. Furthermore, this work was financially supported by the Fundamental Research Funds for the Central Universities (KJQN202060), the National Natural Science Foundation of China (31900907), the Natural Science Foundation of Jiangsu Province (BK20190528) to M.CDeclaration of Interests: The authors of this editorial have no conflicts of interest to declare. The authors have no other relevant affiliations or financial involvement in any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Ethics Approval Statement: This study was approved by the Ethics Committee of Animal Experiments center of Nanjing Agricultural University. All animal studies were approve by the Institutional Animal Care and Use Committee of Nanjing Agricultural University (SYXK-2017-0007), and followed the National Institutes of Health guidelines for the performance of animalexperiments.