Scholarlink

<p>Infections by RNA viruses cause diseases. Host factor(s) that restrain viral propagation offer new anti-virus strategies. We use vesicular stomatitis virus (VSV) as a model and observe the synthesis of VSV RNAs at mitochondria/endoplasmic reticulum (Mito/ER) spheres, accompanied by the leakage of endonuclease G (ENDOG), a mitochondrial nuclease, to the cytosol. We provide evidence that ENDOG released from mitochondria is a host anti-viral factor by eliminating viral RNAs for replication. However, ENDOG outside mitochondria can translocate to nuclei and cause nuclear DNA damages. We engineer an ENDOG expressed on mitochondrial outer membrane (MOM), namely MOM-ENDOG, to increase the accessibility to viral RNA transcripts synthesized at mitochondrial sites without damaging nuclear DNA (nDNA). Delivery of modified mRNA of wild-type but not catalytic-dead MOM-ENDOG markedly suppresses not only the propagation of VSV, but also Dengue and Zika virus. Thus, this organelle-specific viral RNA degrader may be developed as a broad-spectrum anti-viral agent.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

An engineered viral RNA degrader on mitochondrial surface that mitigates RNA virus infection

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月19日

查看全文
  • Chih-Wei Chen,
  • Wei-Ting Liao,
  • Tung Chao,
  • Yi-Han Chen,
  • Shih-Che Weng,
  • Shin-Hong Shiao,
  • Ching-Yang Kao,
  • Yun-Jung Li,
  • Kai-An Cheng,
  • Zee-Fen Chang

摘要

Infections by RNA viruses cause diseases. Host factor(s) that restrain viral propagation offer new anti-virus strategies. We use vesicular stomatitis virus (VSV) as a model and observe the synthesis of VSV RNAs at mitochondria/endoplasmic reticulum (Mito/ER) spheres, accompanied by the leakage of endonuclease G (ENDOG), a mitochondrial nuclease, to the cytosol. We provide evidence that ENDOG released from mitochondria is a host anti-viral factor by eliminating viral RNAs for replication. However, ENDOG outside mitochondria can translocate to nuclei and cause nuclear DNA damages. We engineer an ENDOG expressed on mitochondrial outer membrane (MOM), namely MOM-ENDOG, to increase the accessibility to viral RNA transcripts synthesized at mitochondrial sites without damaging nuclear DNA (nDNA). Delivery of modified mRNA of wild-type but not catalytic-dead MOM-ENDOG markedly suppresses not only the propagation of VSV, but also Dengue and Zika virus. Thus, this organelle-specific viral RNA degrader may be developed as a broad-spectrum anti-viral agent.