Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
Department of Immunology, NHC Key Laboratory of Medical Immunology, Peking University School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Macromol Biosci. 2021 Apr;21(4):e2000382. doi: 10.1002/mabi.202000382. Epub 2021 Feb 1.
Host defense systems can invade viral infection through immune responses and cellular metabolism. Recently, many studies have shown that cellular metabolism can be reprogrammed through N -methyladenosine (m A) modifications during viral infection. Among of them, methyltransferase like-14 enzyme (METTL14) plays an important role in m A RNA modification, yet its antiviral function still remains unclear. In this work, it is uncovered that metal-protein nanoparticles designated GSTP1-MT3(Fe ) (MPNP) can polarize macrophages toward the M1 phenotype and activate immune responses to induce Interferon-beta (IFN-β) production in vesicular stomatitis virus (VSV)-infected macrophages. Further investigation elucidates that a high dose of IFN-β can promote the expression of METTL14, which has a well anti-VSV capacity. Moreover, it is found that other negative-sense single-stranded RNA viruses, such as influenza viruses (H1N1(WSN)), can also be inhibited through either immune responses or METTL14. Collectively, these findings provide insights into the antiviral function of METTL14 and suggest that the manipulation of METTL14 may be a potential strategy to intervene with other negative-sense single-stranded RNA viruses infections.
宿主防御系统可以通过免疫反应和细胞代谢来入侵病毒感染。最近，许多研究表明，细胞代谢可以通过病毒感染过程中的 N -甲基腺苷（m A ）修饰来重新编程。其中，甲基转移酶样 14 酶（METTL14）在 m A RNA 修饰中起着重要作用，但它的抗病毒功能仍不清楚。在这项工作中，发现 GSTP1-MT3(Fe )（MPNP）金属蛋白纳米颗粒可使巨噬细胞向 M1 表型极化，并激活免疫反应，诱导水疱性口炎病毒（VSV）感染的巨噬细胞产生干扰素-β（IFN-β）。进一步的研究表明，高剂量的 IFN-β可以促进 METTL14 的表达，METTL14 具有很好的抗 VSV 能力。此外，还发现其他负义单链 RNA 病毒，如流感病毒（H1N1(WSN)），也可以通过免疫反应或 METTL14 来抑制。总之，这些发现为 METTL14 的抗病毒功能提供了新的见解，并表明操纵 METTL14 可能是干预其他负义单链 RNA 病毒感染的一种潜在策略。
