Adaptive Immune Responses in Humans During Nipah Virus Acute and Convalescent Phases of Infection
Adaptive Immune Responses in Humans During Nipah Virus Acute and Convalescent Phases of Infection
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DOI：
10.1093/cid/ciz010
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发表时间：
2019-11-15
影响因子：
11.8
通讯作者：
Nichol, Stuart T.
中科院分区：
文献类型：
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作者：
Arunkumar, Govindakarnavar;Devadiga, Santhosha;Nichol, Stuart T.
背景。尼帕病毒 (NiV) 是引起国际关注的突发公共卫生事件的 10 种潜在原因之一。我们调查了 2018 年 5 月在印度喀拉拉邦发生的 NiV 疫情。在这里，我们描述了 2 名人类幸存者在急性期和恢复期对 NiV 感染的细胞介导和体液免疫反应的纵向特征。方法。从喀拉拉邦 NiV 疫情中仅有的 2 名幸存者获得了系列血样。我们使用流式细胞术测定 T 淋巴细胞和 B 淋巴细胞的绝对计数以及 T 细胞和 B 细胞的表型。我们还通过病毒特异性免疫球蛋白 M (IgM) 和免疫球蛋白 G (IgG) 酶联免疫吸附测定检测并定量了对 NiV 的体液免疫反应。结果。在两名幸存者的研究期间，T 淋巴细胞的绝对数量始终保持在正常范围内。然而，在这两种情况下都观察到活化的 CD8 T 细胞显着升高。超过 30% 的 CD8 T 细胞表达 Ki67，表明增殖活跃。增殖的 (Ki-67(+)) CD8 T 细胞表达高水平的颗粒酶 B 和 PD-1，与急性效应细胞的特征一致。 NiV 幸存者的总 B 淋巴细胞、活化 B 细胞和浆母细胞计数也有所升高。这些人在发病后一周内产生了可检测的 NiV 特异性 IgM 和 IgG 抗体。 NiV RNA 从血液中的清除先于病毒特异性 IgG 的出现，并且与激活的 CD8 T 细胞的峰值一致。结论。我们首次描述了急性 NiV 感染期间人类 B 细胞和 T 细胞群激活状态的纵向动力学数据。虽然观察到具有效应特征的明显 CD8 T 细胞激活，但激活的 CD4 T 细胞不太明显。
Background. Nipah virus (NiV) is 1 of 10 potential causes of imminent public health emergencies of international concern. We investigated the NiV outbreak that occurred in May 2018 in Kerala, India. Here we describe the longitudinal characteristics of cell-mediated and humoral immune responses to NiV infection during the acute and convalescent phases in 2 human survivors.Methods. Serial blood samples were obtained from the only 2 survivors of the NiV outbreak in Kerala. We used flow cytometry to determine the absolute T-lymphocyte and B-lymphocyte counts and the phenotypes of both T and B cells. We also detected and quantitated the humoral immune response to NiV by virus-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay.Results. Absolute numbers of T lymphocytes remained within normal limits throughout the period of illness studied in both survivors. However, a marked elevation of activated CD8 T cells was observed in both cases. More than 30% of total CD8 T cells expressed Ki67, indicating active proliferation. Proliferating (Ki-67(+)) CD8 T cells expressed high levels of granzyme B and PD-1, consistent with the profile of acute effector cells. Total B-lymphocyte, activated B-cell, and plasmablast counts were also elevated in NiV survivors. These individuals developed detectable NiV-specific IgM and IgG antibodies within a week of disease onset. Clearance of NiV RNA from blood preceded the appearance of virus-specific IgG and coincided with the peak of activated CD8 T cells.Conclusions. We describe for the first time longitudinal kinetic data on the activation status of human B- and T-cell populations during acute NiV infection. While marked CD8 T-cell activation was observed with effector characteristics, activated CD4 T cells were less prominent.