tetano
Editor, Senior Moderator
[h=1]Viral N[SUP]6[/SUP]-methyladenosine upregulates replication and pathogenesis of human respiratory syncytial virus[/h]
[h=2]Abstract[/h] N[SUP]6[/SUP]-methyladenosine (m[SUP]6[/SUP]A) 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 m[SUP]6[/SUP]A within discreet regions and that these modifications enhance viral replication and pathogenesis. Knockdown of m[SUP]6[/SUP]A methyltransferases decreases RSV replication and gene expression whereas knockdown of m[SUP]6[/SUP]A demethylases has the opposite effect. The G gene transcript contains the most m[SUP]6[/SUP]A modifications. Recombinant RSV variants expressing G transcripts that lack particular clusters of m[SUP]6[/SUP]A display reduced replication in A549 cells, primary well differentiated human airway epithelial cultures, and respiratory tracts of cotton rats. One of the m[SUP]6[/SUP]A-deficient variants is highly attenuated yet retains high immunogenicity in cotton rats. Collectively, our results demonstrate that viral m[SUP]6[/SUP]A methylation upregulates RSV replication and pathogenesis and identify viral m[SUP]6[/SUP]A methylation as a target for rational design of live attenuated vaccine candidates for RSV and perhaps other pneumoviruses.
full article
https://www.nature.com/articles/s41...3STSUJ3lhD8SsQAVCGBRILnRfsAL-Zqfw-bG3Nc6ZqEsc
- Miaoge Xue[SUP]1[/SUP],
- Boxuan Simen Zhao[SUP]2[/SUP],
- Zijie Zhang ORCID: orcid.org/0000-0002-4900-506X[SUP]2[/SUP],
- Mijia Lu[SUP]1[/SUP],
- Olivia Harder[SUP]1[/SUP],
- Phylip Chen[SUP]3[/SUP],
- Zhike Lu[SUP]2[/SUP],
- Anzhong Li[SUP]1[/SUP],
- Yuanmei Ma[SUP]1[/SUP],
- Yunsheng Xu[SUP]4[/SUP],
- Xueya Liang[SUP]1[/SUP],
- Jiyong Zhou ORCID: orcid.org/0000-0001-8948-8249[SUP]5[/SUP],
- Stefan Niewiesk[SUP]1[/SUP],
- Mark E. Peeples[SUP]3,6[/SUP],
- Chuan He ORCID: orcid.org/0000-0003-4319-7424[SUP]2,7[/SUP] &
- Jianrong Li[SUP]1[/SUP]
[h=2]Abstract[/h] N[SUP]6[/SUP]-methyladenosine (m[SUP]6[/SUP]A) 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 m[SUP]6[/SUP]A within discreet regions and that these modifications enhance viral replication and pathogenesis. Knockdown of m[SUP]6[/SUP]A methyltransferases decreases RSV replication and gene expression whereas knockdown of m[SUP]6[/SUP]A demethylases has the opposite effect. The G gene transcript contains the most m[SUP]6[/SUP]A modifications. Recombinant RSV variants expressing G transcripts that lack particular clusters of m[SUP]6[/SUP]A display reduced replication in A549 cells, primary well differentiated human airway epithelial cultures, and respiratory tracts of cotton rats. One of the m[SUP]6[/SUP]A-deficient variants is highly attenuated yet retains high immunogenicity in cotton rats. Collectively, our results demonstrate that viral m[SUP]6[/SUP]A methylation upregulates RSV replication and pathogenesis and identify viral m[SUP]6[/SUP]A methylation as a target for rational design of live attenuated vaccine candidates for RSV and perhaps other pneumoviruses.
full article
https://www.nature.com/articles/s41...3STSUJ3lhD8SsQAVCGBRILnRfsAL-Zqfw-bG3Nc6ZqEsc