The Aedes aegypti mosquito is a vector of many infectious agents, including flaviviruses such as Zika virus. Components of mosquito saliva have pleomorphic effects on the vertebrate host to enhance blood feeding, and these changes also create a favorable niche for pathogen replication and dissemination. Here, we demonstrate that human CD47, which is known to be involved in various immune processes, interacts with a 34-kilodalton mosquito salivary protein named Nest1. Nest1 is up-regulated in blood-fed female A. aegypti and facilitates Zika virus dissemination in human skin explants. Nest1 has a stronger affinity for CD47 than its natural ligand, signal regulatory protein α, competing for binding at the same interface. The interaction between Nest1 with CD47 suppresses phagocytosis by human macrophages and inhibits proinflammatory responses by white blood cells, thereby suppressing antiviral responses in the skin. This interaction elucidates how an arthropod protein alters the human response to promote arbovirus infectivity.

中文翻译：

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人 CD47 检查点以免疫抑制埃及伊蚊唾液因子为靶点，以增强虫媒病毒皮肤感染性


埃及伊蚊是许多传染源的媒介，包括寨卡病毒等黄病毒。蚊子唾液的成分对脊椎动物宿主具有多形性作用，以增强血液喂养，这些变化也为病原体的复制和传播创造了有利的生态位。在这里，我们证明了已知参与各种免疫过程的人类 CD47 与一种名为 Nest1 的 34 道尔顿蚊子唾液蛋白相互作用。Nest1 在血液喂养的雌性埃及曲霉中上调，并促进寨卡病毒在人类皮肤外植体中的传播。Nest1 对 CD47 的亲和力比其天然配体信号调节蛋白 α 更强，后者在同一界面竞争结合。Nest1 与 CD47 之间的相互作用抑制了人巨噬细胞的吞噬作用，并抑制了白细胞的促炎反应，从而抑制了皮肤中的抗病毒反应。这种相互作用阐明了节肢动物蛋白如何改变人类反应以促进虫媒病毒传染性。