Assaf B T, Knight H L, Miller A D
Harvard Medical School, New England Primate Research Center, Division of Comparative Pathology, Southborough, MA, USA Oregon Health and Science University, Oregon National Primate Research Center, Division of Pathobiology and Immunology, Beaverton, OR, USA.
Harvard Medical School, New England Primate Research Center, Division of Comparative Pathology, Southborough, MA, USA.
Vet Pathol. 2015 Jan;52(1):217-23. doi: 10.1177/0300985814529313. Epub 2014 Mar 31.
Peripheral neuropathies are common sequelae to human immunodeficiency virus (HIV) infection in humans and are due to a variety of mechanisms, including direct antiretroviral toxicity, HIV-mediated damage, immune-mediated disorders, and opportunistic viral infections. Rhesus macaques (Macaca mulatta) infected with simian immunodeficiency virus (SIV) remain the most consistent animal model for unraveling the pathogenesis of lentiviral-associated disease and its associated opportunistic infections. Rhesus cytomegalovirus (RhCMV) is the most common opportunistic viral infection in rhesus macaques infected with SIV and causes multiorgan pathology; however, its role in peripheral nerve pathology has not been explored. We have identified 115 coinfected cases with SIV and RhCMV, of which 10 cases of RhCMV-associated facial neuritis were found (8.7% prevalence). Histologic lesions were consistent in all cases and ranged from partial to complete obliteration of the nerves of the tongue, lacrimal gland, and other facial tissues with a mixed inflammatory population of neutrophils and macrophages, of which the latter commonly contained intranuclear inclusion bodies. Luxol fast blue staining and myelin basic protein immunohistochemistry confirmed the progressive myelin loss in the peripheral nerves. Bielschowsky silver stain revealed progressive loss of axons directly related to the severity of inflammation. Double immunohistochemistry with spectral imaging analysis revealed RhCMV-infected macrophages directly associated with the neuritis, and there was no evidence to support RhCMV infection of Schwann cells. These results suggest that peripheral nerve damage is a bystander effect secondary to inflammation rather than a direct infection of Schwann cells and warrants further investigations into the pathogenesis of RhCMV-induced peripheral neuropathy.
周围神经病变是人类免疫缺陷病毒（HIV）感染人类后的常见后遗症，其由多种机制引起，包括直接抗逆转录病毒毒性、HIV介导的损伤、免疫介导的紊乱以及机会性病毒感染。感染猿猴免疫缺陷病毒（SIV）的恒河猴（猕猴）仍然是阐明慢病毒相关疾病发病机制及其相关机会性感染的最一致的动物模型。恒河猴巨细胞病毒（RhCMV）是感染SIV的恒河猴中最常见的机会性病毒感染，可导致多器官病变；然而，其在周围神经病变中的作用尚未得到探索。我们确定了115例SIV和RhCMV合并感染病例，其中发现10例RhCMV相关的面神经麻痹（患病率为8.7%）。所有病例的组织学病变一致，范围从舌、泪腺和其他面部组织神经的部分至完全闭塞，伴有中性粒细胞和巨噬细胞混合性炎症细胞浸润，其中后者通常含有核内包涵体。Luxol固蓝染色和髓鞘碱性蛋白免疫组织化学证实周围神经髓鞘进行性丧失。Bielschowsky银染色显示轴突的进行性丧失与炎症严重程度直接相关。光谱成像分析双重免疫组织化学显示RhCMV感染的巨噬细胞与神经炎直接相关，且没有证据支持雪旺细胞感染RhCMV。这些结果表明，周围神经损伤是炎症继发的旁观者效应，而非雪旺细胞的直接感染，值得进一步研究RhCMV诱导的周围神经病变的发病机制。
