Characterizing the Role of Encapsidated Host Ribosomes in Alphavirus Infectivity

描述（由申请方提供）：甲病毒是一组在哺乳动物/禽类宿主和媒介蚊子之间循环传播的相关RNA病毒。甲病毒属的成员因其流行潜力而被公认，并且一些在感染后表现出高死亡率。甲病毒的当代爆发和媒介能力蚊子向未感染人群的持续地理分布强调了对有效抗病毒靶点和疫苗策略的需求。 以前的研究已经描述了哺乳动物和鸟类细胞中产生的甲病毒颗粒;然而，蚊子细胞中产生的颗粒在很大程度上被忽视了。对蚊子来源的辛德毕斯病毒（SINV）的检查表明，宿主核糖体组分被掺入病毒颗粒中。这种现象的表征揭示了宿主核糖体也被掺入哺乳动物衍生的颗粒中，但速率低于对蚊子衍生的颗粒所观察到的速率。有趣的是，发现核糖体腺苷酸化的水平与感染性颗粒的数量相关。 本提案中详细介绍的工作采用多学科方法，包括病毒学、分子、结构和模式生物研究，以表征导致核糖体降解的决定因素和核糖体降解的生物学作用。 这项建议旨在提供一种独特的培训经验，使参与其构想和实施的人员能够继续作为一名独立科学家的职业生涯。

DESCRIPTION (provided by applicant): The Alphaviruses are a group of related RNA viruses that are cyclically transmitted between mammalian / avian hosts and vector mosquitos. Members of the genus Alphavirus are recognized for their epidemic potential and several exhibit high mortality rates upon infection. Contemporary outbreaks of alphaviruses and the ongoing geographical distribution of vector-competent mosquitos towards naive populations underscore the need for effective antiviral targets and vaccine strategies. Previous studies have characterized alphaviral particles produced in mammalian and avian cells; however particles produced in mosquito cells have been largely overlooked. Examination of mosquito derived Sindbis virus (SINV) has indicated that host ribosomal components are incorporated into the viral particles. Characterization of this phenomenon revealed that host ribosomes are incorporated into mammalian derived particles as well, but at a rate less than that observed for mosquito derived particles. Interestingly, the levels of ribosome encapsidation were found to correlate with the number of infectious particles. The work detailed in this proposal uses a multidisciplinary approach consisting of virological, molecular, structural and model organism studies to characterize the determinants leading to and the biological role of ribosome encapsidation. This proposal is designed to provide a unique training experience that will enable those involved in its conceptualization and implementation to continue towards a career as an independent scientist.