PHEV infection: A promising model of betacoronavirus-associated neurological and olfactory dysfunction.
PHEV infection: A promising model of betacoronavirus-associated neurological and olfactory dysfunction.
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PHEV 感染：β冠状病毒相关神经和嗅觉功能障碍的一种有前景的模型
DOI：
10.1371/journal.ppat.1010667
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发表时间：
2022-06
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
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作者：
猪血凝性脑脊髓炎病毒（PHEV）是一种高度嗜神经的冠状病毒，属于β冠状病毒属。与人类易感的病原性冠状病毒（如SARS-CoV-2）相似，PHEV主要通过呼吸道飞沫和密切接触传播，从初始感染部位的外周神经进入中枢神经系统（CNS）。然而，PHEV的神经侵袭途径知之甚少。在此，我们发现BALB/c小鼠对鼻内PHEV感染易感，并表现出不同的神经学表现。行为学研究和组织病理学检查表明，PHEV攻击中枢神经系统的神经元，并导致小鼠明显的嗅觉和味觉功能障碍。通过追踪神经侵袭，我们确定PHEV通过位于鼻腔的嗅神经和三叉神经侵入CNS，并且嗅感觉神经元（OSNs）对病毒感染敏感。免疫荧光染色和超微结构观察显示，病毒物质沿沿着轴突，表明轴突运输可能参与病毒在中枢神经系统中的快速传播。此外，嗅觉系统和CNS中的病毒复制与炎症和免疫应答、组织紊乱和功能障碍相关。总的来说，我们认为PHEV可能作为阐明冠状病毒相关神经系统并发症以及嗅觉和味觉障碍发病机制的潜在原型。PHEV是一种嗜神经性猪β冠状病毒（β-CoV），主要在哺乳猪的呼吸道和CNS中感染和复制。神经系统并发症和嗅觉丧失（即，无法感知气味或嗅觉功能丧失）是冠状病毒引起的疾病的常见临床特征，但其潜在机制仍不清楚。在这项研究中，我们研究了神经和嗅觉功能障碍的发病机制，在小鼠模型的PHEV感染。数据强调PHEV通过嗅觉和三叉神经侵入CNS，并且嗅觉丧失和神经系统表现与直接OSN感染和神经免疫炎症相关。PHEV原型的利用将为未来研究人类致病性冠状病毒的神经侵袭和神经发病机制提供平台。
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic coronavirus belonging to the genus Betacoronavirus. Similar to pathogenic coronaviruses to which humans are susceptible, such as SARS-CoV-2, PHEV is transmitted primarily through respiratory droplets and close contact, entering the central nervous system (CNS) from the peripheral nerves at the site of initial infection. However, the neuroinvasion route of PHEV are poorly understood. Here, we found that BALB/c mice are susceptible to intranasal PHEV infection and showed distinct neurological manifestations. The behavioral study and histopathological examination revealed that PHEV attacks neurons in the CNS and causes significant smell and taste dysfunction in mice. By tracking neuroinvasion, we identified that PHEV invades the CNS via the olfactory nerve and trigeminal nerve located in the nasal cavity, and olfactory sensory neurons (OSNs) were susceptible to viral infection. Immunofluorescence staining and ultrastructural observations revealed that viral materials traveling along axons, suggesting axonal transport may engage in rapid viral transmission in the CNS. Moreover, viral replication in the olfactory system and CNS is associated with inflammatory and immune responses, tissue disorganization and dysfunction. Overall, we proposed that PHEV may serve as a potential prototype for elucidating the pathogenesis of coronavirus-associated neurological complications and olfactory and taste disorders. PHEV, a neurotropic porcine betacoronavirus (β-CoV), primarily infects and replicates in the respiratory tract and CNS in suckling pigs. Neurological complications and anosmia (i.e., inability to perceive odor or loss of olfactory function) are common clinical features in coronavirus-induced diseases, however the underlying mechanisms remain unclear. In this study, we investigated the pathogenesis of neurological and olfactory dysfunction in a murine model of PHEV infection. The data underscore that PHEV invades the CNS via the olfactory and trigeminal nerves, and that anosmia and neurological manifestations are associated with direct OSNs infection and neuroimmune inflammation. The utilization of PHEV prototype will provide a platform for future studies on the neuroinvasion and neuropathogenesis of human pathogenic coronaviruses.
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DOI：
10.1126/science.abd3072
发表时间：
2020-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Daly JL;Simonetti B;Klein K;Chen KE;Williamson MK;Antón-Plágaro C;Shoemark DK;Simón-Gracia L;Bauer M;Hollandi R;Greber UF;Horvath P;Sessions RB;Helenius A;Hiscox JA;Teesalu T;Matthews DA;Davidson AD;Collins BM;Cullen PJ;Yamauchi Y
通讯作者：
Yamauchi Y
影响因子：
0.8
作者：
Hirano N;Nomura R;Tawara T;Tohyama K
通讯作者：
Tohyama K
鉴定与 PHE-CoV 刺突蛋白相互作用的 NCAM
影响因子：
4.8
作者：
Gao W;He W;Zhao K;Lu H;Ren W;Du C;Chen K;Lan Y;Song D;Gao F
通讯作者：
Gao F
影响因子：
28.3
作者：
Gorbalenya, Alexander E.;Baker, Susan C.;Ziebuhr, John
通讯作者：
Ziebuhr, John
影响因子：
2.5
作者：
BURD, GD
通讯作者：
BURD, GD