PDF(Pubmed)
Abstract：
Enterovirus D68 (EV-D68) is predominantly associated with mild respiratory infections, but can also cause severe respiratory disease and extra-respiratory complications, including acute flaccid myelitis. Systemic dissemination of EV-D68 is crucial for the development of extra-respiratory diseases, but it is currently unclear how EV-D68 spreads systemically (viremia). We hypothesize that immune cells contribute to the systemic dissemination of EV-D68, as this is a mechanism commonly used by other enteroviruses. Therefore, we investigated the susceptibility and permissiveness of human primary immune cells for different EV-D68 isolates. In human peripheral blood mononuclear cells inoculated with EV-D68, only B cells were susceptible but virus replication was limited. However, in B cell-rich cultures, such as Epstein-Barr virus-transformed B-lymphoblastoid cell line (BLCL) and primary lentivirus-transduced B cells, which better represent lymphoid B cells, were productively infected. Subsequently, we showed that dendritic cells (DCs), particularly immature DCs, are susceptible and permissive for EV-D68 infection and that they can spread EV-D68 to autologous BLCL. Altogether, our findings suggest that immune cells, especially B cells and DCs, could play an important role in the pathogenesis of EV-D68 infection. Infection of these cells may contribute to systemic dissemination of EV-D68, which is an essential step toward the development of extra-respiratory complications.IMPORTANCEEnterovirus D68 (EV-D68) is an emerging respiratory virus that has caused outbreaks worldwide since 2014. EV-D68 infects primarily respiratory epithelial cells resulting in mild respiratory diseases. However, EV-D68 infection is also associated with extra-respiratory complications, including polio-like paralysis. It is unclear how EV-D68 spreads systemically and infects other organs. We hypothesized that immune cells could play a role in the extra-respiratory spread of EV-D68. We showed that EV-D68 can infect and replicate in specific immune cells, that is, B cells and dendritic cells (DCs), and that virus could be transferred from DCs to B cells. Our data reveal a potential role of immune cells in the pathogenesis of EV-D68 infection. Intervention strategies that prevent EV-D68 infection of immune cells will therefore potentially prevent systemic spread of virus and thereby severe extra-respiratory complications.
摘要：
肠道病毒D68（EV-D68）主要与轻度呼吸道感染有关，但也会导致严重的呼吸系统疾病和呼吸道外并发症，包括急性弛缓性脊髓炎.EV-D68的系统传播对于呼吸道外疾病的发展至关重要，但目前尚不清楚EV-D68如何系统性传播（病毒血症）。我们假设免疫细胞有助于EV-D68的全身传播，因为这是其他肠道病毒常用的机制。因此,我们调查了人类原代免疫细胞对不同EV-D68分离株的易感性和允许性.在接种EV-D68的人外周血单核细胞中，只有B细胞易感，但病毒复制有限。然而,在富含B细胞的培养物中，例如EB病毒转化的B淋巴母细胞细胞系（BLCL）和原代慢病毒转导的B细胞，更好地代表淋巴B细胞，被生产性感染。随后，我们发现树突状细胞(DCs),特别是不成熟的DC，易感且允许EV-D68感染，并且它们可以将EV-D68传播到自体BLCL。总之,我们的研究结果表明，免疫细胞，尤其是B细胞和DC,可能在EV-D68感染的发病机制中起重要作用。这些细胞的感染可能有助于EV-D68的全身扩散，这是发展呼吸道外并发症的重要步骤。IMPORTANCE肠病毒D68（EV-D68）是一种新兴的呼吸道病毒，自2014年以来已在全球范围内引起疫情。EV-D68主要感染呼吸道上皮细胞,导致轻度呼吸道疾病。然而,EV-D68感染也与呼吸道外并发症有关，包括脊髓灰质炎样瘫痪。目前尚不清楚EV-D68如何全身传播并感染其他器官。我们假设免疫细胞可能在EV-D68的呼吸道外传播中起作用。我们表明EV-D68可以感染并在特定的免疫细胞中复制，也就是说,B细胞和树突状细胞（DC），病毒可以从DC转移到B细胞。我们的数据揭示了免疫细胞在EV-D68感染的发病机理中的潜在作用。因此,防止免疫细胞的EV-D68感染的干预策略将潜在地防止病毒的全身传播,从而防止严重的呼吸道外并发症。
