Details

Autor(en) / Beteiligte

• Xue, Miaoge
• Zhao, Boxuan Simen
• Zhang, Zijie
• Lu, Mijia
• Harder, Olivia
• Chen, Phylip
• Lu, Zhike
• Li, Anzhong
• Ma, Yuanmei
• Xu, Yunsheng
• Liang, Xueya
• Zhou, Jiyong
• Niewiesk, Stefan
• Peeples, Mark E
• He, Chuan
• Li, Jianrong

Titel

Viral N 6 -methyladenosine upregulates replication and pathogenesis of human respiratory syncytial virus

Ist Teil von

• Nature communications, 2019-10, Vol.10 (1), p.4595-18

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• N -methyladenosine (m 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 A within discreet regions and that these modifications enhance viral replication and pathogenesis. Knockdown of m A methyltransferases decreases RSV replication and gene expression whereas knockdown of m A demethylases has the opposite effect. The G gene transcript contains the most m A modifications. Recombinant RSV variants expressing G transcripts that lack particular clusters of m A display reduced replication in A549 cells, primary well differentiated human airway epithelial cultures, and respiratory tracts of cotton rats. One of the m A-deficient variants is highly attenuated yet retains high immunogenicity in cotton rats. Collectively, our results demonstrate that viral m A methylation upregulates RSV replication and pathogenesis and identify viral m A methylation as a target for rational design of live attenuated vaccine candidates for RSV and perhaps other pneumoviruses.