Direct Infection of B Cells by Dengue Virus Modulates B Cell Responses in a Cambodian Pediatric Cohort.
Direct Infection of B Cells by Dengue Virus Modulates B Cell Responses in a Cambodian Pediatric Cohort.
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DOI：
10.3389/fimmu.2020.594813
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发表时间：
2020
影响因子：
7.3
通讯作者：
Cantaert T
中科院分区：
文献类型：
--
作者：
Upasani V;Vo HTM;Auerswald H;Laurent D;Heng S;Duong V;Rodenhuis-Zybert IA;Dussart P;Cantaert T
登革热是一种由登革病毒（DENV）引起的急性病毒性疾病，由伊蚊传播。登革病毒感染的症状从无症状到严重不等，可能危及生命。登革病毒在树突状细胞和巨噬细胞等初级免疫细胞中复制，这有助于病毒的传播。其他免疫细胞（如B细胞）对登革病毒直接感染的易感性及其感染后的反应尚未明确界定。在一组60名柬埔寨儿童中，我们发现B细胞易受登革病毒感染。此外，我们表明B细胞能够支持实验室适应株和患者来源的登革病毒株的病毒复制。B细胞允许登革病毒感染，尽管在细胞上清液中释放的感染性病毒粒子滴度较低。CD300a是一种磷脂酰丝氨酸受体，被确定为登革病毒进入B细胞的潜在附着因子或受体。尽管表达Fcγ受体，但在体外模型中未观察到B细胞中抗体介导的登革病毒感染增强。登革病毒的直接感染在体内诱导登革热患者的B细胞增殖，并在体外诱导浆母细胞/浆细胞形成。总之，我们的研究结果表明，B细胞易通过CD300a受到登革病毒的直接感染，随后的B细胞反应可能有助于登革热的发病机制。
Dengue is an acute viral disease caused by dengue virus (DENV), which is transmitted by Aedes mosquitoes. Symptoms of DENV infection range from inapparent to severe and can be life-threatening. DENV replicates in primary immune cells such as dendritic cells and macrophages, which contribute to the dissemination of the virus. Susceptibility of other immune cells such as B cells to direct infection by DENV and their subsequent response to infection is not well defined. In a cohort of 60 Cambodian children, we showed that B cells are susceptible to DENV infection. Moreover, we show that B cells can support viral replication of laboratory adapted and patient-derived DENV strains. B cells were permissive to DENV infection albeit low titers of infectious virions were released in cell supernatants CD300a, a phosphatidylserine receptor, was identified as a potential attachment factor or receptor for entry of DENV into B cells. In spite of expressing Fcγ-receptors, antibody-mediated enhancement of DENV infection was not observed in B cells in an in vitro model. Direct infection by DENV induced proliferation of B cells in dengue patients in vivo and plasmablast/plasma cell formation in vitro. To summarize, our results show that B cells are susceptible to direct infection by DENV via CD300a and the subsequent B cell responses could contribute to dengue pathogenesis.