The Phosphatidylserine and Phosphatidylethanolamine Receptor CD300a Binds Dengue Virus and Enhances Infection
The Phosphatidylserine and Phosphatidylethanolamine Receptor CD300a Binds Dengue Virus and Enhances Infection
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DOI：
10.1128/jvi.01849-15
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发表时间：
2016-01-01
影响因子：
5.4
通讯作者：
Amara, Ali
中科院分区：
文献类型：
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作者：
Carnec, Xavier;Meertens, Laurent;Amara, Ali
登革病毒(DENV)是引起人类主要虫媒病毒病的病原体。我们先前已经证明，参与细胞吞噬的磷脂酰丝氨酸受体TIM和家族参与了DENV进入靶细胞的过程。我们在这里表明，人CD300a，一种最近发现的磷脂受体，也直接与DENV颗粒结合，并增强病毒进入。CD300a有助于感染四种DENV血清型以及其他蚊媒病毒，如西尼罗河病毒和基孔肯雅病毒。CD300a作为一种附着因子，通过网状蛋白介导的内吞作用增强DENV的内化作用。CD300a主要识别磷脂酰乙醇胺(PtdEth)，少量识别与病毒颗粒相关的PtdSer。磷脂结合阻断CD300a介导的DENV感染增强关键的免疫球蛋白结构域残基突变。最后，我们发现CD300a在原代巨噬细胞表面表达，抗CD300a多克隆抗体部分抑制了DENV对这些细胞的感染。总之，这些数据表明CD300a是一种新的DENV结合受体，它识别存在于病毒粒子上的PtdEth和PtdSer，并增强感染。
Dengue virus (DENV) is the etiological agent of the major human arboviral disease. We previously demonstrated that the TIM and TAM families of phosphatidylserine (PtdSer) receptors involved in the phagocytosis of apoptotic cells mediate DENV entry into target cells. We show here that human CD300a, a recently identified phospholipid receptor, also binds directly DENV particles and enhances viral entry. CD300a facilitates infection of the four DENV serotypes, as well as of other mosquito-borne viruses such as West Nile virus and Chikungunya virus. CD300a acts as an attachment factor that enhances DENV internalization through clathrin-mediated endocytosis. CD300a recognizes predominantly phosphatidylethanolamine (PtdEth) and to a lesser extent PtdSer associated with viral particles. Mutation of residues in the IgV domain critical for phospholipid binding abrogate CD300a-mediated enhancement of DENV infection. Finally, we show that CD300a is expressed at the surface of primary macrophages and anti-CD300a polyclonal antibodies partially inhibited DENV infection of these cells. Overall, these data indicate that CD300a is a novel DENV binding receptor that recognizes PtdEth and PtdSer present on virions and enhance infection.