Abstract
Background METTL3 (methyltransferase like 3) and FTO (fat mass and obesity-associated protein) are critical for establishing and regulating the m6A (N6-methyladenosine) modification, but very little is known about the function of m6A in the immune system or its role in interactions within the host immune system.
Methods Western blotting experiment was used to check the expression of the host proteins related to m6A modification after H7N9 influenza virus infection. Immunofluorescence experiment was used to identify whether the subcellular localization of related proteins. Moreover, we knocked down and over express endogenous METTL3 or FTO in A549 cells, and then infected the cells with H7N9 to test whether methyltransferases or demethylases affect H7N9 replication.
Result We confirmed that the expression pattern of m6A proteins was altered during H7N9 infection. METTL3 and FTO were located in the nucleus, and YTHDF3 was located in the cytoplasm. Furthermore, our results demonstrate that downregulation of METTL3 or FTO expression in A549 cells severely impairs viral protein expression and H7N9 infection.
Conclusions METTL3 and FTO are critical for H7N9 replication which may represent a new mechanism for the control of H7N9 replication and host-pathogen interactions.
Keywords
References
Qi W, Jia W, Liu D, et al. Emergence and Adaptation of a Novel Highly Pathogenic H7N9 Influenza Virus in Birds and Humans from a 2013 Human-Infecting Low-Pathogenic Ancestor. J Virol. 2018 Jan 2;92(2):e00921-17. doi: 10.1128/JVI.00921-17.
Shen Y, Lu H. Global concern regarding the fifth epidemic of human infection with avian influenza A (H7N9) virus in China. Biosci Trends. 2017;11(1):120-121. doi:10.5582/bst.2017.01040.[
Bouvier NM, Palese P. The biology of influenza viruses. Vaccine. 2008;26 Suppl 4(Suppl 4):D49-D53. doi:10.1016/j.vaccine.2008.07.039.
Schöller E, Weichmann F, Treiber T, et al. Interactions, localization, and phosphorylation of the m6A generating METTL3-METTL14-WTAP complex. RNA. 2018; 24(4):499-512. doi:10.1261/rna.064063.117Jia.
Jia G, Fu Y, Zhao X, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO [published correction appears in Nat Chem Biol. 2012 Dec;8(12):1008]. Nat Chem Biol. 2011;7(12):885-887. Published 2011 Oct 16. doi:10.1038/nchembio.687.
Zheng G, Dahl JA, Niu Y, et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell. 2013;49(1):18-29. doi:10.1016/j.molcel.2012.10.015.
He C. Grand challenge commentary: RNA epigenetics?. Nat Chem Biol. 2010;6(12):863-865. doi:10.1038/nchembio.482.
Pizzi M. Sampling variation of the fifty percent end-point, determined by the Reed-Muench (Behrens) method. Hum Biol. 1950;22(3):151-190.
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