Neuroinvasion by human respiratory coronaviruses
Neuroinvasion by human respiratory coronaviruses
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DOI：
10.1128/jvi.74.19.8913-8921.2000
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发表时间：
2000-10-01
影响因子：
5.4
通讯作者：
Talbot, PJ
中科院分区：
文献类型：
--
作者：
Arbour, N;Day, R;Talbot, PJ
人类冠状病毒(HCoV)会导致普通感冒，但也可以感染神经细胞培养物。为了对人类冠状病毒的嗜神经性和神经侵袭性及其与多发性硬化症(MS)的可能联系提供明确的实验证据，我们在大量的人脑尸检样本中进行了HCoV RNA的广泛搜索和表征。对90例神经系统疾病患者(MS患者39例，其他神经系统疾病患者26例)和正常对照组(25例)进行了非常严格的逆转录-聚合酶链式反应(229E和OC43)。我们报告，34%(40/90)的捐献者仅229E呈阳性，而23%(21/90)的捐献者OC43呈阳性。MS患者OC43的患病率(35.9%，14/39)显著高于对照组(13.7%，7/51)。核衣壳蛋白(N)基因扩增序列显示OC43有点突变，其中一些在三名MS患者和一名正常对照中一致发现，但从未在实验室病毒中观察到。原位杂交证实病毒RNA存在于血管外的脑实质中。人脑中HCoV的存在与这些呼吸道病原体对神经的侵袭是一致的。需要进一步的研究来区分人脑中存在的机会性病毒和与疾病相关的病毒。
Human coronaviruses (HCoV) cause common colds but can also infect neural cell cultures. To provide definitive experimental evidence for the neurotropism and neuroinvasion of HCoV and its possible association with multiple sclerosis (MS), we have performed an extensive search and characterization of HCoV RNA in a large panel of human brain autopsy samples. Very stringent reverse transcription-PCR,vith two primer pairs for both viral strains (229E and OC43), combined with Southern hybridization, was performed on samples from 90 coded donors with various neurological diseases (39 with MS and 26 with other neurological diseases) or normal controls (25 patients). We report that 34% (40 of 90) of donors mere positive for 229E and that 23% (21 of 90) were positive for OC43. A statistically significant higher prevalence of OC43 in MS patients (35.9%; 14 of 39) than in controls (13.7%; 7 of 51) was observed. Sequencing of nucleocapsid protein (N) gene amplicons revealed point mutations in OC43, some consistently found in three MS patient brains and one normal control but never observed in laboratory viruses. In situ hybridization confirmed the presence of viral RNA in brain parenchyma, outside blood vessels. The presence of HCoV in human brains is consistent with neuroinvasion by these respiratory pathogens. Further studies are needed to distinguish between opportunistic and disease-associated viral presence in human brains.