Human Norovirus Triggers Primary B Cell Immune Activation In Vitro.
Human Norovirus Triggers Primary B Cell Immune Activation In Vitro.
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人类诺如病毒（HNoV）是一种全球性的健康和社会经济负担，估计每个人一生中至少感染五次。对HNoV感染缺乏长期免疫保护的潜在机制尚不清楚，这促使我们研究原代人B细胞的HNoV易感性及其功能影响。用HNoV阳性粪便样品感染从全血分离的原代B细胞，并在感染后3天（dpi）收获，以通过逆转录酶定量PCR（RT-qPCR）评估病毒RNA产量。在50%至60%的供体中观察到HNoV RNA产量增加3至18倍。在脾和淋巴结活检标本来源的B细胞中进一步证实了感染。接下来，我们通过流式细胞术在特定功能性B细胞亚群（初始CD 27 − IgD+、记忆转换CD 27 + IgD−、记忆非转换CD 27 + IgD+和双阴性CD 27 − IgD−细胞）中表征了全血来源的B细胞的感染。虽然亚群的亲和性相似，但观察到感染后B细胞亚群分布的变化，这在用HNoV病毒样颗粒和预测的重组NS 1蛋白处理后也被注意到。重要的是，用预测的重组NS 1蛋白刺激原代B细胞触发B细胞活化并诱导代谢变化。这些数据表明，原代B细胞对HNoV感染敏感，并表明NS 1蛋白可以在体外改变B细胞活化和代谢，这可能对体内病毒发病机制和免疫应答有影响。
Human norovirus (HNoV) is a global health and socioeconomic burden, estimated to infect every individual at least five times during their lifetime. The underlying mechanism for the potential lack of long-term immune protection from HNoV infections is not understood and prompted us to investigate HNoV susceptibility of primary human B cells and its functional impact. Primary B cells isolated from whole blood were infected with HNoV-positive stool samples and harvested at 3 days postinfection (dpi) to assess the viral RNA yield by reverse transcriptase quantitative PCR (RT-qPCR). A 3- to 18-fold increase in the HNoV RNA yield was observed in 50 to 60% of donors. Infection was further confirmed in B cells derived from splenic and lymph node biopsy specimens. Next, we characterized infection of whole-blood-derived B cells by flow cytometry in specific functional B cell subsets (naive CD27− IgD+, memory-switched CD27+ IgD−, memory-unswitched CD27+ IgD+, and double-negative CD27− IgD− cells). While the susceptibilities of the subsets were similar, changes in the B cell subset distribution upon infection were observed, which were also noted after treatment with HNoV virus-like particles and the predicted recombinant NS1 protein. Importantly, primary B cell stimulation with the predicted recombinant NS1 protein triggered B cell activation and induced metabolic changes. These data demonstrate that primary B cells are susceptible to HNoV infection and suggest that the NS1 protein can alter B cell activation and metabolism in vitro, which could have implications for viral pathogenesis and immune responses in vivo.
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影响因子：
30.3
作者：
Lee S;Wilen CB;Orvedahl A;McCune BT;Kim KW;Orchard RC;Peterson ST;Nice TJ;Baldridge MT;Virgin HW
通讯作者：
Virgin HW
影响因子：
15.3
作者：
Moir, Susan;Ho, Jason;Fauci, Anthony S.
通讯作者：
Fauci, Anthony S.
影响因子：
6.7
作者：
Van Dycke, Jana;Ny, Annelii;Rocha-Pereira, Joana
通讯作者：
Rocha-Pereira, Joana
DOI：
10.1073/pnas.1014577107
发表时间：
2011-01-04
影响因子：
11.1
作者：
Bok, Karin;Parra, Gabriel I.;Green, Kim Y.
通讯作者：
Green, Kim Y.
DOI：
10.1084/jem.188.9.1691
发表时间：
1998-11-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Tangye SG;Liu YJ;Aversa G;Phillips JH;de Vries JE
通讯作者：
de Vries JE