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实验性再激活后,恒河猴淋巴结中的巨噬细胞、树突状细胞和T细胞中存在猴水痘病毒。

Simian Varicella Virus Is Present in Macrophages, Dendritic Cells, and T Cells in Lymph Nodes of Rhesus Macaques after Experimental Reactivation.

作者信息

Traina-Dorge Vicki, Doyle-Meyers Lara A, Sanford Robert, Manfredo Jennifer, Blackmon Anna, Wellish Mary, James Stephanie, Alvarez Xavier, Midkiff Cecily, Palmer Brent E, Deharo Eileen, Gilden Don, Mahalingam Ravi

机构信息

Division of Microbiology, Tulane University, Tulane National Primate Research Center, Covington, Louisiana, USA.

Division of Veterinary Medicine, Tulane University, Tulane National Primate Research Center, Covington, Louisiana, USA.

出版信息

J Virol. 2015 Oct;89(19):9817-24. doi: 10.1128/JVI.01324-15. Epub 2015 Jul 15.

Abstract

UNLABELLED

Like varicella-zoster virus (VZV), simian varicella virus (SVV) reactivates to produce zoster. In the present study, 5 rhesus macaques were inoculated intrabronchially with SVV, and 5 months later, 4 monkeys were immunosuppressed; 1 monkey was not immunosuppressed but was subjected to the stress of transportation. In 4 monkeys, a zoster rash developed 7 to 12 weeks after immunosuppression, and a rash also developed in the monkey that was not immunosuppressed. Analysis at 24 to 48 h after zoster revealed SVV antigen in the lung alveolar wall, in ganglionic neurons and nonneuronal cells, and in skin and in lymph nodes. In skin, SVV was found primarily in sweat glands. In lymph nodes, the SVV antigen colocalized mostly with macrophages, dendritic cells, and, to a lesser extent, T cells. The presence of SVV in lymph nodes, as verified by quantitative PCR detection of SVV DNA, might reflect the sequestration of virus by macrophages and dendritic cells in lymph nodes or the presentation of viral antigens to T cells to initiate an immune response against SVV, or both.

IMPORTANCE

VZV causes varicella (chickenpox), becomes latent in ganglia, and reactivates to produce zoster and multiple other serious neurological disorders. SVV in nonhuman primates has proved to be a useful model in which the pathogenesis of the virus parallels the pathogenesis of VZV in humans. Here, we show that SVV antigens are present in sweat glands in skin and in macrophages and dendritic cells in lymph nodes after SVV reactivation in monkeys, raising the possibility that macrophages and dendritic cells in lymph nodes serve as antigen-presenting cells to activate T cell responses against SVV after reactivation.

摘要

未标记

与水痘带状疱疹病毒(VZV)一样,猴水痘病毒(SVV)再激活会引发带状疱疹。在本研究中,5只恒河猴经支气管内接种SVV,5个月后,4只猴子接受免疫抑制;1只猴子未接受免疫抑制,但遭受了运输应激。在4只接受免疫抑制的猴子中,免疫抑制7至12周后出现带状疱疹皮疹,未接受免疫抑制的猴子也出现了皮疹。带状疱疹出现后24至48小时的分析显示,SVV抗原存在于肺泡壁、神经节神经元和非神经元细胞、皮肤和淋巴结中。在皮肤中,SVV主要存在于汗腺中。在淋巴结中,SVV抗原大多与巨噬细胞、树突状细胞共定位,在较小程度上与T细胞共定位。通过对SVV DNA进行定量PCR检测证实,淋巴结中存在SVV,这可能反映了巨噬细胞和树突状细胞在淋巴结中对病毒的隔离,或者病毒抗原呈递给T细胞以引发针对SVV的免疫反应,或者两者兼而有之。

重要性

VZV引起水痘(水痘),潜伏在神经节中,再激活会引发带状疱疹和多种其他严重的神经系统疾病。已证明非人类灵长类动物中的SVV是一种有用的模型,其中该病毒的发病机制与人类VZV的发病机制相似。在这里,我们表明,猴子中SVV再激活后,SVV抗原存在于皮肤的汗腺以及淋巴结中的巨噬细胞和树突状细胞中,这增加了淋巴结中的巨噬细胞和树突状细胞作为抗原呈递细胞在再激活后激活针对SVV的T细胞反应的可能性。

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