Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, 97006, USA.
Sci Rep. 2017 Apr 20;7(1):937. doi: 10.1038/s41598-017-01051-5.
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.
人巨细胞病毒（HCMV）具有严格的种属特异性，这阻碍了我们在人类免疫系统背景下理解抗病毒适应性免疫反应。我们之前已经表明，在免疫缺陷小鼠（huNSG）中移植的人造血祖细胞中 HCMV 的感染会导致潜伏感染，这种潜伏感染可以在 G-CSF 治疗后被重新激活。在这项研究中，我们描述了潜伏感染 HCMV 的人源化骨髓-肝-胸腺（huBLT）小鼠中的功能性人类适应性免疫反应。感染后，huBLT 小鼠产生针对 IE 和 pp65 蛋白的肽段的人效应和中央记忆 CD4+和 CD8+T 细胞反应。此外，还检测到能够中和病毒的 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潜伏感染和再激活以及在功能性人类免疫系统背景下评估 HCMV 疫苗和免疫反应提供了有价值的工具。
