Measles virus replication in lymphatic cells and organs of CD150 (SLAM) transgenic mice.

Measles virus replication in lymphatic cells and organs of CD150 (SLAM) transgenic mice.
复制标题

麻疹病毒在 CD150 (SLAM) 转基因小鼠的淋巴细胞和器官中复制。

DOI:
10.1073/pnas.0505945102
复制
发表时间:
2005
影响因子:
11.1
通讯作者:
C. Richardson
C. Richardson
中科院分区:
综合性期刊1区
文献类型:
--
作者:
G. Welstead;Caterina Iorio;R. Draker;J. Bayani;J. Squire;S. Vongpunsawad;R. Cattaneo;C. Richardson;C. Richardson

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通过使用克隆到细菌人工染色体中的人基因组DNA产生含有完整的人SLAM(hSLAM/CD 150)基因(包括其用于转录的内源性启动子)的转基因小鼠。麻疹病毒(MV)的主要受体hSLAM在活化的B、T和树突状细胞上表达,其表达谱与人的表达谱相当。我们证明了从转基因小鼠中获得的hSLAM(+)细胞,包括活化的B、T和树突状细胞,以受体依赖的方式对MV感染敏感。提供了hSLAM(+)小鼠鼻内接种后鼻淋巴结中瞬时感染的证据。病毒被迅速清除,没有二次复制的迹象。为了提高MV生产的效率,将hSLAM(+)小鼠与具有Stat 1缺陷背景的小鼠交配。这些小鼠更容易感染MV,并产生更多的病毒颗粒。这些小鼠经鼻和腹腔接种MV后,检测到胸腺、脾脏、鼻、肠系膜和腿部淋巴结的感染。尸检时,淋巴结和脾脏明显肿大。流式细胞术分析显示,异常大量的成熟中性粒细胞和自然杀伤细胞引起脾肿大。hSLAM转基因小鼠构成了用于研究MV与免疫细胞的相互作用的改进的啮齿动物模型,其更准确地反映了在人类中发现的感染模式。
A transgenic mouse containing the complete human SLAM (hSLAM/CD150) gene, including its endogenous promoter for transcription, was generated by using human genomic DNA cloned into a bacterial artificial chromosome. hSLAM, the primary receptor for measles viruses (MV), was expressed on activated B, T, and dendritic cells with an expression profile equivalent to that of humans. We demonstrated that hSLAM(+) cells obtained from the transgenic mouse, including activated B, T, and dendritic cells, were susceptible to MV infection in a receptor-dependent manner. Evidence was provided for transient infection in the nasal lymph nodes of hSLAM(+) mice after intranasal inoculation. Virus was rapidly cleared without signs of secondary replication. To improve the efficiency of MV production, the hSLAM(+) mice were bred with mice having a Stat1-deficient background. These mice were more susceptible to MV infection and produced more virus particles. After intranasal and intraperitoneal inoculation of these mice with MV, infections of the thymus, spleen, nasal, mesenteric, and leg lymph nodes were detected. Upon necropsy, enlarged lymph nodes and spleen were apparent. Flow cytometric analysis showed that abnormally large numbers of mature neutrophils and natural killer cells caused the splenomegaly. The hSLAM transgenic mouse constitutes an improved rodent model for studying the interaction of MV with immune cells that more accurately reflects the infection pattern found in humans.
重组麻疹减毒活疫苗载体可引发有效的 HLA-A0201 限制性细胞毒性 T 淋巴细胞和针对 HIV-1 保守表位的广泛中和抗体。
DOI: 10.1016/j.vaccine.2005.04.024
发表时间: 2005
期刊: Vaccine
影响因子: 5.5
作者:
Lorin,Clarisse;Delebecque,Frédéric;Labrousse,Valérie;DaSilva,Lucie;Lemonnier,François;Brahic,Michel;Tangy,Frédéric
通讯作者: Tangy,Frédéric
DOI: 10.1016/j.virol.2004.03.011
发表时间: 2004-06-01
期刊: VIROLOGY
影响因子: 3.7
作者:
Hahm, B;Arbour, N;Oldstone, MBA
通讯作者: Oldstone, MBA