Mir M A, Duran W A, Hjelle B L, Ye C, Panganiban A T
Department of Molecular Genetics, Cancer Research Facility University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19294-9. doi: 10.1073/pnas.0807211105. Epub 2008 Dec 1.
The minus strand and ambisense segmented RNA viruses include multiple important human pathogens and are divided into three families, the Orthomyxoviridae, the Bunyaviridae, and the Arenaviridae. These viruses all initiate viral transcription through the process of "cap-snatching," which involves the acquisition of capped 5' oligonucleotides from cellular mRNA. Hantaviruses are emerging pathogenic viruses of the Bunyaviridae family that replicate in the cytoplasm of infected cells. Cellular mRNAs can be actively translated in polysomes or physically sequestered in cytoplasmic processing bodies (P bodies) where they are degraded or stored for subsequent translation. Here we show that the hantavirus nucleocapsid protein binds with high affinity to the 5' cap of cellular mRNAs, protecting the 5' cap from degradation. We also show that the hantavirus nucleocapsid protein accumulates in P bodies, where it sequesters protected 5' caps. P bodies then serve as a pool of primers during the initiation of viral mRNA synthesis by the viral polymerase. We propose that minus strand segmented viruses replicating in the cytoplasm have co-opted the normal degradation machinery of P bodies for storage of cellular caps. Our data also indicate that modification of the cap-snatching model is warranted to include a role for the nucleocapsid protein in cap acquisition and storage.
负链和双义分段RNA病毒包括多种重要的人类病原体，分为三个科，即正粘病毒科、布尼亚病毒科和沙粒病毒科。这些病毒均通过“帽抢夺”过程启动病毒转录，该过程涉及从细胞mRNA获取带帽的5'寡核苷酸。汉坦病毒是布尼亚病毒科中新兴的致病病毒，在受感染细胞的细胞质中复制。细胞mRNA可在多核糖体中被积极翻译，或被物理隔离在细胞质加工体（P小体）中，在那里它们被降解或储存以供后续翻译。在此我们表明，汉坦病毒核衣壳蛋白与细胞mRNA的5'帽以高亲和力结合，保护5'帽不被降解。我们还表明，汉坦病毒核衣壳蛋白在P小体中积累，在那里它隔离受保护的5'帽。然后，P小体在病毒聚合酶启动病毒mRNA合成期间充当引物池。我们提出，在细胞质中复制的负链分段病毒已利用P小体的正常降解机制来储存细胞帽。我们的数据还表明，有必要对帽抢夺模型进行修正，以纳入核衣壳蛋白在帽获取和储存中的作用。
