Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice.
Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice.
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DOI：
10.1016/j.jaut.2012.11.005
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发表时间：
2013-05
影响因子：
12.8
通讯作者：
Blackman MA
中科院分区：
文献类型：
--
作者：
Freeman ML;Burkum CE;Lanzer KG;Roberts AD;Pinkevych M;Itakura A;Kummer LW;Szaba FM;Davenport MP;McCarty OJ;Woodland DL;Smiley ST;Blackman MA
人类疱疹病毒建立终身潜伏期。病毒复发可导致癌症、免疫增殖性疾病、移植并发症和血小板减少症的发展。虽然血小板特异性自身抗体已被报道在感染EB病毒（EBV）的患者中，血小板减少症诱导的机制仍不清楚，裂解性病毒复制和潜伏性病毒基因表达的相对贡献。人类γ疱疹病毒感染其他哺乳动物的能力受到严格限制，因此很难在活体动物模型中进行研究。在这里，我们表明，小鼠感染鼠γ疱疹病毒-68（γ HV 68），一种与EBV密切相关的啮齿动物特异性病原体，诱导血小板结合抗体的产生并引起血小板减少症。抗体缺陷型小鼠感染后不引起血小板减少，表明血小板减少是由抗体介导的。此外，无潜伏期重组γ HV 68感染不会诱导血小板减少症，表明与病毒潜伏期相关的因素驱动感染诱导的抗体介导的血小板减少症。这些研究描述了一个重要的动物模型，γ疱疹病毒诱导的自身免疫性血小板减少症，并证明这种病理是由抗体介导的，并依赖于病毒的潜伏期。该模型将允许研究疾病进展的潜在机制，并测试缓解病毒诱导的血小板减少症的治疗策略。
Human herpesviruses establish lifelong latency. Viral recrudescence can lead to the development of cancers, immunoproliferative disorders, transplantation complications, and thrombocytopenia. Although platelet-specific autoantibodies have been reported in patients infected with the Epstein-Barr virus (EBV), the mechanisms by which thrombocytopenia is induced remain unclear, as do the relative contributions of lytic viral replication and latent viral gene expression. The human gammaherpesviruses are tightly restricted in their ability to infect other mammals, so they are difficult to study in live animal models. Here we show that infection of mice with murine gammaherpesvirus-68 (γHV68), a rodent-specific pathogen closely related to EBV, induces the production of platelet-binding antibodies and causes thrombocytopenia. Infection of antibody-deficient mice does not lead to thrombocytopenia, indicating the platelet decrease is mediated by antibody. Additionally, infection with a latency-null recombinant γHV68 does not induce thrombocytopenia, suggesting factors associated with viral latency drive the infection-induced antibody-mediated thrombocytopenia. These studies describe an important animal model of gammaherpesvirus-induced autoimmune thrombocytopenia and demonstrate that this pathology is mediated by antibody and dependent on viral latency. This model will allow studies of the underlying mechanisms of disease progression and the testing of therapeutic strategies for the alleviation of virus-induced thrombocytopenia.
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