Human Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune Responses in Humanized BLT Mice.
Human Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune Responses in Humanized BLT Mice.
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DOI：
10.1038/s41598-017-01051-5
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发表时间：
2017-04-20
影响因子：
4.6
通讯作者：
Caposio P
中科院分区：
文献类型：
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作者：
Crawford LB;Tempel R;Streblow DN;Kreklywich C;Smith P;Picker LJ;Nelson JA;Caposio P
人类巨细胞病毒（HCMV）严格的物种特异性阻碍了我们对人类免疫系统背景下的抗病毒适应性免疫反应的理解。我们之前已经证明，移植到免疫缺陷小鼠 (huNSG) 中的人类造血祖细胞的 HCMV 感染会导致病毒潜伏，在 G-CSF 治疗后可以重新激活。在这项研究中，我们表征了 HCMV 潜伏感染的 huBLT（人源化骨髓-肝脏-胸腺）小鼠的功能性人类适应性免疫反应。感染后，huBLT 小鼠产生人类效应细胞和中央记忆 CD4+ 和 CD8+ T 细胞反应，对 IE 和 pp65 蛋白对应的肽有反应。此外，还检测到具有中和病毒能力的 HCMV 特异性 IgM 和 IgG B 细胞反应。这些结果表明，HCMV huBLT 小鼠模型可能为研究病毒潜伏和重新激活以及在功能性人类免疫系统的背景下评估 HCMV 疫苗和免疫反应提供有价值的工具。
The strict species specificity of Human Cytomegalovirus (HCMV) has impeded our understanding of antiviral adaptive immune responses in the context of a human immune system. We have previously shown that HCMV infection of human hematopoietic progenitor cells engrafted in immune deficient mice (huNSG) results in viral latency that can be reactivated following G-CSF treatment. In this study, we characterized the functional human adaptive immune responses in HCMV latently-infected huBLT (humanized Bone marrow-Liver-Thymus) mice. Following infection, huBLT mice generate human effector and central memory CD4+ and CD8+ T-cell responses reactive to peptides corresponding to both IE and pp65 proteins. Additionally, both HCMV specific IgM and IgG B-cell responses with the ability to neutralize virus were detected. These results indicate that the HCMV huBLT mouse model may provide a valuable tool to study viral latency and reactivation as well as evaluate HCMV vaccines and immune responses in the context of a functional human immune system.