New Cornerstone Science Laboratory, Tsinghua University-Peking University Joint Center for Life Sciences, School of Basic Medical Sciences, Tsinghua University, Beijing, 100084, China.
Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, 518000, China.
EMBO J. 2024 May;43(9):1690-1721. doi: 10.1038/s44318-024-00056-x. Epub 2024 Feb 20.
Mosquitoes transmit many disease-relevant flaviviruses. Efficient viral transmission to mammalian hosts requires mosquito salivary factors. However, the specific salivary components facilitating viral transmission and their mechanisms of action remain largely unknown. Here, we show that a female mosquito salivary gland-specific protein, here named A. aegypti Neutrophil Recruitment Protein (AaNRP), facilitates the transmission of Zika and dengue viruses. AaNRP promotes a rapid influx of neutrophils, followed by virus-susceptible myeloid cells toward mosquito bite sites, which facilitates establishment of local infection and systemic dissemination. Mechanistically, AaNRP engages TLR1 and TLR4 of skin-resident macrophages and activates MyD88-dependent NF-κB signaling to induce the expression of neutrophil chemoattractants. Inhibition of MyD88-NF-κB signaling with the dietary phytochemical resveratrol reduces AaNRP-mediated enhancement of flavivirus transmission by mosquitoes. These findings exemplify how salivary components can aid viral transmission, and suggest a potential prophylactic target.
蚊子传播许多与疾病相关的黄病毒。要将病毒有效地传播给哺乳动物宿主，需要蚊子的唾液因子。然而，促进病毒传播的特定唾液成分及其作用机制在很大程度上仍然未知。在这里，我们表明，一种雌性蚊子唾液腺特异性蛋白，即埃及伊蚊嗜中性粒细胞募集蛋白（AaNRP），促进了寨卡病毒和登革热病毒的传播。AaNRP 促进了中性粒细胞的快速涌入，随后是对蚊子叮咬部位具有易感性的髓样细胞，从而有利于局部感染和系统传播的建立。从机制上讲，AaNRP 与皮肤常驻巨噬细胞上的 TLR1 和 TLR4 结合，并激活 MyD88 依赖性 NF-κB 信号通路，诱导中性粒细胞趋化因子的表达。用膳食植物化学物质白藜芦醇抑制 MyD88-NF-κB 信号通路，可减少蚊子介导的 AaNRP 对黄病毒传播的增强作用。这些发现说明了唾液成分如何帮助病毒传播，并为潜在的预防性治疗靶点提供了思路。
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