N6-Methyladenosine and Viral Infection.

Jia Wang,Jianhong Lu,Wei Dang,Yanling Li,Shuyu Xin,Shen Li,Yan Xie,Pengfei Cao

doi:10.3389/fmicb.2019.00417

Jia Wang, Jianhong Lu + Show 6 more

Open Access

https://doi.org/10.3389/fmicb.2019.00417

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Abstract

N6-methyladenosine (m6A), as a dynamic posttranscriptional RNA modification, recently gave rise to the field of viral epitranscriptomics. The interaction between virus and host is affected by m6A. Multiple m6A-modified viral RNAs have been observed. The epitranscriptome of m6A in host cells are altered after viral infection. The expression of viral genes, the replication of virus and the generation of progeny virions are influenced by m6A modifications in viral RNAs during virus infection. Meanwhile, the decorations of m6A in host mRNAs can make viral infections more likely to happen or can enhance the resistance of host to virus infection. However, the mechanism of m6A regulation in viral infection and host immune response has not been thoroughly elucidated to date. With the development of sequencing-based biotechnologies, transcriptome-wide mapping of m6A in viruses has been achieved, laying the foundation for expanding its functions and corresponding mechanisms. In this report, we summarize the positive and negative effects of m6A in distinct viral infection. Given the increasingly important roles of m6A in diverse viruses, m6A represents a novel potential target for antiviral therapy.

Highlights

Among the diverse layers of epigenetic regulation, modifications of DNA and proteins have been explored in depth; RNA modification is a relatively new field (He, 2010)
The Kaposi’s Sarcoma-Associated Herpesvirus (KSHV)-positive renal carcinoma cell line iSLK.219 during lytic reactivation went through transcriptome-wide m6A-sequencing, and the results revealed that the m6A modification was present across most viral transcripts
M6A suppressed ORF50 protein expression in KSHV infected B cells. m6A induced faster viral replication, and larger viral plaques in BSC40 cells infected with Simian Virus 40 (SV40). m6A located in Hepatitis B Virus (HBV) 3 untranslated regions (3 UTRs) and 3 epsilon loop reduced the stability of these RNAs

Summary

INTRODUCTION

Among the diverse layers of epigenetic regulation, modifications of DNA and proteins have been explored in depth; RNA modification is a relatively new field (He, 2010). A study reported that YTHDC2 lacked the m6A binding activity in HEK cells (Patil et al, 2016, 2018) This finding suggests that YTHDC2 might have indirect effects in regulating m6A-modified RNAs through interaction with other factors. As the first virus found to express mRNAs bearing internal m6A groups, Influenza A virus (IAV) was mapped for the sites of m6A by Courtney et al in both the IAV mRNA and vRNA strands, and it was demonstrated that m6A modification increases viral RNA expression in cis (Courtney et al, 2017) Those authors used two methods to inhibit m6A modification in A549 cells infected by IAV.

Mechanisms of action

Cell types used

IAV HCV

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