Virus Host Interaction Team, Leeds Institute of Medical Research, School of Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, LS9 7TF, United Kingdom.
MRC-University of Glasgow Centre for Virus Research, Glasgow, G61 1QH, Scotland, United Kingdom.
Proc Natl Acad Sci U S A. 2022 Jun 14;119(24):e2114309119. doi: 10.1073/pnas.2114309119. Epub 2022 Jun 8.
Viruses transmitted by mosquitoes are an increasingly important global cause of disease. Defining common determinants of host susceptibility to this large group of heterogenous pathogens is key for informing the rational design of panviral medicines. Infection of the vertebrate host with these viruses is enhanced by mosquito saliva, a complex mixture of salivary-gland-derived factors and microbiota. We show that the enhancement of infection by saliva was dependent on vascular function and was independent of most antisaliva immune responses, including salivary microbiota. Instead, the gene product sialokinin mediated the enhancement of virus infection through a rapid reduction in endothelial barrier integrity. Sialokinin is unique within the insect world as having a vertebrate-like tachykinin sequence and is absent from , which are incompetent for most arthropod-borne viruses, whose saliva was not proviral and did not induce similar vascular permeability. Therapeutic strategies targeting sialokinin have the potential to limit disease severity following infection with -mosquito-borne viruses.
通过蚊子传播的病毒是日益重要的全球性疾病病因。明确宿主对这组异质病原体易感性的共同决定因素，对于合理设计泛病毒药物至关重要。这些病毒感染脊椎动物宿主会受到蚊子唾液的促进，蚊子唾液是一种由唾液腺衍生因子和微生物群组成的复杂混合物。我们发现，唾液对感染的促进作用依赖于血管功能，并且不依赖于大多数抗唾液免疫反应，包括唾液微生物群。相反，神经肽 sialokinin 通过迅速降低内皮屏障完整性来介导病毒感染的增强。神经肽 sialokinin 在昆虫世界中是独一无二的，因为它具有类似脊椎动物的速激肽序列，而在 中则不存在， 对大多数节肢动物传播的病毒没有作用，其唾液不促进病毒感染，也不会诱导类似的血管通透性。针对 sialokinin 的治疗策略有可能限制感染 - 蚊子传播病毒后的疾病严重程度。
