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Viral N6-methyladenosine upregulates replication and pathogenesis of human respiratory syncytial virus
- Source :
- Nature Communications, Nature Communications, Vol 10, Iss 1, Pp 1-18 (2019)
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- N6-methyladenosine (m6A) is the most prevalent internal modification of mRNAs in most eukaryotes. Here we show that RNAs of human respiratory syncytial virus (RSV) are modified by m6A within discreet regions and that these modifications enhance viral replication and pathogenesis. Knockdown of m6A methyltransferases decreases RSV replication and gene expression whereas knockdown of m6A demethylases has the opposite effect. The G gene transcript contains the most m6A modifications. Recombinant RSV variants expressing G transcripts that lack particular clusters of m6A display reduced replication in A549 cells, primary well differentiated human airway epithelial cultures, and respiratory tracts of cotton rats. One of the m6A-deficient variants is highly attenuated yet retains high immunogenicity in cotton rats. Collectively, our results demonstrate that viral m6A methylation upregulates RSV replication and pathogenesis and identify viral m6A methylation as a target for rational design of live attenuated vaccine candidates for RSV and perhaps other pneumoviruses.<br />Here, Xue et al. identify N6-methyladenosine (m6A) modification sites in RNAs of respiratory syncytial virus (RSV) and show that these sites, particularly sites in the transcript encoding for the viral glycoprotein, affect virus replication in primary human cells and cotton rats.
- Subjects :
- Male
0301 basic medicine
Adenosine
Methyltransferase
Live attenuated vaccines
Science
viruses
General Physics and Astronomy
Respiratory Syncytial Virus Infections
Biology
Virus-host interactions
Antibodies, Viral
Vaccines, Attenuated
Virus Replication
Article
General Biochemistry, Genetics and Molecular Biology
Virus
03 medical and health sciences
0302 clinical medicine
Chlorocebus aethiops
Gene expression
Respiratory Syncytial Virus Vaccines
Animals
Humans
Sigmodontinae
lcsh:Science
Vero Cells
Gene knockdown
Multidisciplinary
Attenuated vaccine
Virulence
General Chemistry
Methylation
Virology
Up-Regulation
3. Good health
030104 developmental biology
Viral replication
Viral infection
A549 Cells
Respiratory Syncytial Virus, Human
030220 oncology & carcinogenesis
Vero cell
RNA
lcsh:Q
Female
HeLa Cells
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....d4f93c91efb08b6dc9cb5c3352c869ae