Related Experiment Video
Updated: Jun 6, 2025
Exploring m6A and m5C Epitranscriptomes upon Viral Infection: an Example with HIV
Published on: March 5, 2022
N6-methyladenosine RNA modification promotes Severe Fever with Thrombocytopenia Syndrome Virus infection
Zhiqiang Chen1,2, Jinyu Zhang1, Jun Wang1
1Jiangsu Key Laboratory of Infection and Immunity, MOE Key Laboratory of Geriatric Diseases and Immunology, The Forth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, China.
Abstract:
Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV), a novel bunyavirus primarily transmitted by Haemaphysalis longicornis, induces severe disease with a high mortality rate. N6-methyladenosine (m6A) is a prevalent internal chemical modification in eukaryotic mRNA that has been reported to regulate viral infection. However, the role of m6A modification during SFTSV infection remains elusive. We here reported that SFTSV RNAs bear m6A modification during infection. Manipulating the expressions or activities of host m6A regulators significantly impacted SFTSV infection. Mechanistically, SFTSV recruited m6A regulators through the nucleoprotein to modulate the m6A modification of viral RNA, eventually resulting in enhanced infection by promoting viral mRNA translation efficiency and/or genome RNA stability. m6A mutations in the S genome diminished virus particle production, while m6A mutations in the G transcript impaired the replication of recombinant vesicular stomatitis virus (rVSV) expressing G protein in vitro and in vivo. Interestingly, m6A modification was evolutionarily conserved and facilitated SFTSV infection in primary tick cells. These findings may open an avenue for the development of m6A-targeted anti-SFTSV vaccines, drugs, and innovative strategies for the prevention and control of tick-borne disease.
Insights
Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) infection is modulated by N6-methyladenosine (m6A) RNA modification. SFTSV hijacks host m6A regulators to enhance viral translation and stability, offering new therapeutic targets.
Area of Science:
- Virology
- Molecular Biology
- Epigenetics
Background:
- Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) causes severe illness and high mortality.
- N6-methyladenosine (m6A) is a key mRNA modification influencing viral infections.
- The role of m6A in SFTSV pathogenesis was previously unknown.
Purpose of the Study:
- To investigate the role of m6A modification in SFTSV infection.
- To elucidate the mechanisms by which m6A affects SFTSV replication.
- To explore m6A as a potential therapeutic target for SFTSV.
Main Methods:
- Analysis of m6A modification on SFTSV RNA during infection.
- Manipulation of host m6A regulator expression and activity.
- Site-directed mutagenesis of m6A sites in SFTSV RNA.
- Assessment of viral replication in cell culture and tick cells.
Main Results:
- SFTSV RNAs exhibit m6A modification during infection.
- Host m6A regulators significantly impact SFTSV replication.
- SFTSV recruits host m6A regulators via its nucleoprotein to enhance viral mRNA translation and genome stability.
- m6A modifications are conserved and promote SFTSV infection in tick cells.
Conclusions:
- m6A modification plays a crucial role in SFTSV infection by enhancing viral replication.
- Targeting m6A regulators presents a promising strategy for developing anti-SFTSV therapeutics and control measures.
- Findings open avenues for m6A-targeted vaccines and drugs against tick-borne diseases.
Related Concept Videos
02:23RNA Editing
01:29Viruses with RNA Genomes
02:28Leaky Scanning
02:36Transfer RNA Synthesis
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
02:30siRNA - Small Interfering RNAs
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
02:31Nuclear Export of mRNA