Molecular and cellular aspects of the life cycle of multipartite viruses: nanoviruses

新出现的植物病毒是全世界的威胁。详细研究它们的生命周期是揭示替代控制策略的先决条件。我们将以纳米病毒科为目标，既有实际的原因，也有根本的原因：i)它对Musaceae作物（Babuvirus属）和豆类（Nanovirus属）构成巨大威胁，ii)它采用了神秘的“多部”组织，其基因组由几个核酸片段组成，每个核酸片段都单独被封壳。纳米病毒是迄今为止所描述的基因组片段数量最多的多部分病毒，它们是研究植物病毒最常采用的这种病毒基因组结构特异性过程的完美模型。特别是，这些病毒如何能够有效地感染高比例的细胞/宿主，其中每个细胞/宿主的众多基因组片段至少有一个拷贝，仍然是难以捉摸的。这被认为是不可能的，在文献中，实际上质疑的概念框架，我们试图理解多部病毒系统。我们最近一致地表明，纳米病毒并不以符合当前病毒学概念的方式发挥作用。病毒在宿主的不同个体细胞中传播不同的基因组片段。这些片段在细胞间功能互补，从而定义了一种多细胞的生活方式。这一病毒学上前所未有的发现现在需要深入研究，以破译允许这种令人惊讶的病毒生活方式的机制。更具体地说，Krenz小组分析了病毒蛋白在病毒与宿主相互作用中的作用，而Blanc小组研究了宿主内病毒种群动态和植物间传播过程中病毒与载体的相互作用。通过这个项目，我们将联合起来研究整个生命周期。我们建议破译与寄主植物和蚜虫载体相互作用的各种纳米病毒基因产物的生化和生物学特性。我们的目标是了解不同的病毒基因组片段最初在不同的植物细胞中表达的实际功能，它们如何在远距离和超细胞尺度上进行交流和互补。我们将分析病毒基因产物的特性，重点关注那些功能未知的基因产物，以及可能参与细胞间转运以进行互补的基因产物。同样，我们将努力了解病毒颗粒如何成功地穿过蚜虫载体的身体，确保所有片段都被获取，运输穿过蚜虫的细胞屏障，并一起接种。因此，除了迫切需要更好地了解纳米病毒的生物学特性之外，这个项目的另一个雄心勃勃的目标是破译多体病毒维持多细胞生活方式的方法，从而肯定地将这一发现作为植物病毒学和其他领域的新研究领域。

Emerging plant viruses are a threat worldwide. Studying their life cycles in details is a prerequisite to reveal alternative control strategies. We will target the family Nanoviridae for both practical and fundamental reasons: i) it represents a huge threat for Musaceae crop (genus Babuvirus) and for legumes (genus Nanovirus), and ii) it has adopted the enigmatic “multipartite” organization, with its genome composed of several nucleic acid segments each encapsidated individually. Nanoviruses being multipartite viruses with the highest number of genome segments described thus far, they are perfect models to investigate processes that might be specific to this viral genomic architecture most frequently adopted by plant viruses. In particular, how such viruses can efficiently infect a high proportion of cells/hosts with at least one copy of each of their numerous genome segments remains elusive. It is deemed impossible in the literature that actually questions the conceptual frame with which we try to comprehend the multipartite viral systems. Consistently, we recently showed that a nanovirus do not function in a way that fits the current concepts in virology. The virus spreads distinct genome segments in distinct individual cells of the host. These segments functionally complement across cells and thereby define a pluricellular way of life. This unprecedented discovery in virology now requires in depth investigation to decipher the mechanisms allowing such a surprising viral lifestyle. More specifically the Krenz group analyzes the viral proteins role during virus-host interactions, while the Blanc group studies the within-host viral population dynamics and the virus-vector interactions during plant-to-plant transmission. Through this project, we will join forces to study the full lifecycle. We propose to decipher the biochemical and biological properties of various nanoviral gene products interacting with host plants and aphid vectors. We aim to understand how distinct viral genome segments initially expressed in distinct plant cells actually function, how they can communicate and complement at a distance and at a supra-cellular scale. We will analyze the properties of the viral gene products with a focus on those with yet unknown function, and on properties that could be involved in trafficking among cells for complementation. Likewise, we will strive to understand how virus particles successfully travel through the body of their aphid vectors, ensuring that all segments are acquired, transported across aphid’s cell barriers, and inoculated together. Thus, beyond the urgent need to better understand the biology of nanoviruses, an emerging threat worldwide, another ambitious goal of this project is to decipher the means by which a multipartite virus can sustain a pluricellular lifestyle, and thereby definitely coin this discovery as a new research horizon in plant virology and beyond.