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Newcastle disease virus activates methylation-related enzymes to reprogram m6A methylation in infected cells

文献类型： 外文期刊

作者： Yuan, Weifeng 1 ; Hou, Yuechi 1 ; Wang, Qingyi 1 ; Lv, Ting 1 ; Ren, Jinlian 1 ; Fan, Lei 1 ; Cai, Juncheng 1 ; Xiang, Bin 5 ; Lin, Qiuyan 1 ; Liao, Ming 6 ; Ding, Chan 7 ; Chen, Libin 1 ; Ren, Tao 1 ;

作者机构： 1.South China Agr Univ, Coll Vet Med, Guangzhou 510642, Peoples R China

2.Natl & Reg Joint Engn Lab Medicament Zoonosis Prev, Guangzhou, Peoples R China

3.Minist Agr, Key Lab Anim Vaccine Dev, Guangzhou, Peoples R China

4.Key Lab Zoonosis Prevent & Control Guangdong Prov, Guangzhou, Peoples R China

5.Yunnan Agr Univ, Coll Vet Med, Kunming 650201, Yunnan, Peoples R China

6.Guangdong Acad Agr Sci, Inst Anim Hlth, Guangzhou 510640, Peoples R China

7.Chinese Acad Agr Sci CAAS, Shanghai Vet Res Inst SHVRI, Shanghai 200241, Peoples R China

关键词： Newcastle disease virus; N6-methyladenosine; MeRIP-Seq; M6A; Methyltransferase

期刊名称：VETERINARY MICROBIOLOGY （ 影响因子：3.3； 五年影响因子：3.5 ）

ISSN： 0378-1135

年卷期： 2023 年 281 卷

页码：

收录情况： SCI

摘要： Newcastle disease virus (NDV) is a paramyxovirus with high incidence and transmissibility in birds and is currently being developed for cancer therapy. N6-methyladenosine (m6A) is a common epigenetic modification of RNA. In this study, we aimed to determine whether this modification plays an important role in NDV infection. We found that methylation-related enzymes were activated in NDV-infected cells, and the abundance of m6A notably increased in vivo and in vitro. Further functional experiments showed that m6A methylation negatively regulates NDV infection. Methylated RNA immunoprecipitation sequencing revealed that the m6A-methylated peaks on different functional components of host genes shifted, underwent reprogramming, and were primarily enriched in the coding sequence after NDV infection. The differentially modified genes were mainly enriched in cellular components, as well as autophagy and ubiquitination-mediated proteolysis signaling pathways. Asso-ciation analysis of RNA sequencing results showed changes in m6A regulated mRNA transcription and revealed that YTHDC1 is a methylation-related enzyme with important catalytic and recognition roles during NDV infection. Additionally, m6A-methylated peaks were detected in the NDV genome, which may be regulated by methylation-related enzymes in the host, subsequently affecting viral replication. Comprehensive analysis of the m6A expression profile after NDV infection indicated that NDV may cause reprogramming of m6A methylation and that m6A plays important roles during infection. Overall, these findings provide insights into the epigenetic etiology and pathogenesis of NDV.

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