In vitro Studies and Clinical Observations Imply a Synergistic Effect Between Epstein-Barr Virus and Dengue Virus Infection.
In vitro Studies and Clinical Observations Imply a Synergistic Effect Between Epstein-Barr Virus and Dengue Virus Infection.
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体外研究和临床观察表明 Epstein-Barr 病毒和登革热病毒感染之间存在协同作用
DOI：
10.3389/fmicb.2021.691008
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发表时间：
2021
影响因子：
5.2
通讯作者：
Xu P
中科院分区：
文献类型：
--
作者：
Deng XM;Zhao LZ;Liang XY;Li D;Yu L;Zhang FC;Zhang H;Liu ZY;Xu P
登革病毒（DENV）感染可导致一系列复杂的临床结果，从无症状感染到危及生命的严重登革。这种疾病表现如此剧烈变化的原因仍然是一个谜。在此，我们报告了先前存在的EB病毒（EBV）感染和登革病毒体外重叠感染之间的协同效应以及这两种病毒在登革热患者临床样本中的强相关性的原始发现。我们显示（I）EBV阳性细胞系（EBV + Akata细胞）的DENV-2感染重新激活EBV，并且它可以被渥曼青霉素处理阻断。(II)对来自登革热患者的人外周血单核细胞（PBMC）样本的检查显示，在大多数个体中，住院时与疾病恢复时相比，细胞相关的EBV DNA拷贝数显著升高。(III)EBV感染促进了DENV在EBV宿主B细胞中的增殖，并间接促进了THP-1细胞中的增殖，这得到了以下证据的支持：（A）与不携带EBV病毒的Akata细胞（EBV-Akata细胞）相比，EBV + Akata细胞更容许DENV-2感染。(B)从EBV + Akata细胞分泌的低分子量组分可增强DENV-2在单核细胞THP-1细胞中的增殖。(C)虽然EBV + Akata细胞中EBV的再活化进一步增加了来自该细胞系的DENV-2产量，但阿昔洛韦对EBV复制的药理学抑制具有相反的效果。据我们所知，这是第一次研究表明，在体外和人类生物标本中EBV和DENV之间的正相关性。
Dengue virus (DENV) infection can lead to a complex spectrum of clinical outcomes, ranging from asymptomatic infection to life-threatening severe dengue. The reasons for thus drastically varying manifestations of the disease remain an enigma. Herein, we reported an original discovery of the synergistic effect between preexisting Epstein–Barr virus (EBV) infection and DENV superinfection in vitro and of a strong correlation of these two viruses in the clinical samples from dengue patients. We showed that (I) DENV-2 infection of an EBV-positive cell line (EBV + Akata cell) reactivated EBV, and it could be blocked by wortmannin treatment. (II) Examination of human peripheral blood mononuclear cell (PBMC) samples from dengue patients revealed significantly elevated cell-associated EBV DNA copy number at the time of hospitalization vs. at the time of disease recovery in most individuals. (III) EBV infection promoted DENV propagation in both EBV-hosting B cells and indirectly in THP-1 cells, supported by the following evidence: (A) EBV + Akata cells were more permissive to DENV-2 infection compared with Akata cells harboring no EBV virus (EBV- Akata cells). (B) Low-molecular weight fraction secreted from EBV + Akata cells could enhance DENV-2 propagation in monocytic THP-1 cells. (C) While reactivation of EBV in EBV + Akata cells further increased DENV-2 yield from this cell line, pharmacological inhibition of EBV replication by acyclovir had the opposite effect. To our knowledge, this is the first investigation demonstrating a positive correlation between EBV and DENV in vitro and in human biospecimens.
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影响因子：
7.6
作者：
Goswami R;Gershburg S;Satorius A;Gershburg E
通讯作者：
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