Terhzaz Selim, Kerrigan David, Almire Floriane, Szemiel Agnieszka M, Hughes Joseph, Parvy Jean-Philippe, Palmarini Massimo, Kohl Alain, Shi Xiaohong, Pondeville Emilie
MRC-University of Glasgow Centre for Virus Research, Glasgow, G61 1QH, Scotland, UK.
Departments of Tropical Disease Biology and Vector Biology, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.
Nat Commun. 2025 Jan 31;16(1):1214. doi: 10.1038/s41467-024-54809-7.
Bunyavirales is a very large order including viruses infecting a variety of taxonomic groups such as arthropods, vertebrates, plants, and protozoa. Some bunyaviruses are transmitted between vertebrate hosts by blood-sucking arthropods and cause major diseases in humans and animals. It is not understood why only some bunyaviruses have evolved the capacity to be transmitted by arthropod vectors. Here we show that only vector-borne bunyaviruses express a non-structural protein, NSm, whose function has so far remained largely elusive. Using as experimental system Bunyamwera virus (BUNV) and its invertebrate host, Aedes aegypti, we show that NSm is dispensable for viral replication in mosquito cells in vitro but is absolutely required for successful infection in the female mosquito following a blood meal. More specifically, NSm is required for cell-to-cell spread and egress from the mosquito midgut, a known barrier to viral infection. Notably, the requirement for NSm is specific to the midgut; bypassing this barrier by experimental intrathoracic infection of the mosquito eliminates the necessity of NSm for virus spread in other tissues, including the salivary glands. Overall, we unveiled a key evolutionary process that allows the transmission of vector-borne bunyaviruses between arthropod and vertebrate hosts.
布尼亚病毒目是一个非常大的目，包括感染各种分类群的病毒，如节肢动物、脊椎动物、植物和原生动物。一些布尼亚病毒通过吸血节肢动物在脊椎动物宿主之间传播，并在人类和动物中引起重大疾病。目前尚不清楚为什么只有一些布尼亚病毒进化出了通过节肢动物载体传播的能力。在这里，我们表明，只有媒介传播的布尼亚病毒才表达一种非结构蛋白NSm，其功能迄今仍 largely 难以捉摸。我们使用布尼亚姆韦拉病毒（BUNV）及其无脊椎动物宿主埃及伊蚊作为实验系统，表明NSm在体外蚊子细胞中的病毒复制中是可有可无的，但在雌性蚊子吸食血液后成功感染中是绝对必需的。更具体地说，NSm是细胞间传播和从蚊子中肠逸出所必需的，中肠是病毒感染的已知屏障。值得注意的是，对NSm的需求仅限于中肠；通过对蚊子进行实验性胸腔内感染绕过这一屏障，消除了NSm在病毒在包括唾液腺在内的其他组织中传播的必要性。总体而言，我们揭示了一个关键的进化过程，该过程允许媒介传播的布尼亚病毒在节肢动物和脊椎动物宿主之间传播。
