Visser Imke, Vaes Vincent, van Run Peter, Marshall Eleanor M, Vermaat Lars, Linthout Charlotte, Dekkers Dick H W, Demmers Jeroen A A, Koopmans Marion P G, Koenraadt Constantianus J M, Rissmann Melanie, Rockx Barry
Department of Viroscience, Erasmus University Medical Center, Rotterdam, the Netherlands.
Erasmus Laboratory Animal Science Center, Erasmus University Medical Center, Rotterdam, The Netherlands.
Emerg Microbes Infect. 2025 Dec;14(1):2502006. doi: 10.1080/22221751.2025.2502006. Epub 2025 Jun 20.
During probing and feeding, an infected mosquito injects both virus and saliva into the host skin. The presence of mosquito saliva in the skin increases arbovirus pathogenesis in the bitten host, however the exact mechanism behind this remains to be determined. It is hypothesized that disease enhancement is dependent on the function of the dermal endothelium, where increased permeability aids in the influx of virus-susceptible cells to the bite site and therefore more cells for the virus to replicate in. Here, we investigate the effects of saliva from and species on human dermal endothelial cell function . Furthermore, we investigate the effect of saliva on West Nile virus (WNV) pathogenesis in a mouse model. We found that salivary gland extract from anthropophilic mosquito species ( and ) induce permeability of the human dermal endothelium, while an ornithophilic mosquito species () does not. We identified that this effect is likely due to the presence of protease(s) in saliva that are absent in saliva. In addition, we show that presence of saliva at the WNV inoculation site leads to more consistent weight loss, increased permeability of the dermal endothelium at the inoculation site, and increased mortality compared to inoculation of WNV alone. Identification and characterization of novel salivary proteins from similar but genetically distinct mosquito species will advance the development of intervention methods to combat potential transmission risks and disease severity of emerging mosquito-borne pathogens.
在刺叮和取食过程中，受感染的蚊子会将病毒和唾液都注入宿主皮肤。皮肤中存在蚊子唾液会增加虫媒病毒在叮咬宿主中的致病性，然而其背后的确切机制仍有待确定。据推测，疾病增强依赖于真皮内皮细胞的功能，内皮细胞通透性增加有助于病毒易感细胞流入叮咬部位，从而为病毒提供更多可复制的细胞。在此，我们研究了[具体蚊子种类1]和[具体蚊子种类2]的唾液对人真皮内皮细胞功能的影响。此外，我们还研究了[具体蚊子种类3]的唾液对小鼠模型中西尼罗河病毒（WNV）发病机制的影响。我们发现，嗜人血蚊子种类（[具体蚊子种类1]和[具体蚊子种类2]）的唾液腺提取物会诱导人真皮内皮细胞的通透性，而嗜鸟血蚊子种类（[具体蚊子种类3]）则不会。我们确定这种影响可能是由于[具体蚊子种类1]唾液中存在蛋白酶，而[具体蚊子种类3]唾液中没有。此外，我们还表明，与单独接种WNV相比，在WNV接种部位存在[具体蚊子种类1]的唾液会导致更持续的体重减轻、接种部位真皮内皮细胞通透性增加以及死亡率上升。对相似但基因不同的蚊子种类的新型唾液蛋白进行鉴定和表征，将推动干预方法的开发，以应对新出现的蚊媒病原体的潜在传播风险和疾病严重程度。
