Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.
mSphere. 2024 Feb 28;9(2):e0052623. doi: 10.1128/msphere.00526-23. Epub 2024 Jan 23.
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.
肠道病毒 D68（EV-D68）主要与轻度呼吸道感染有关，但也可引起严重的呼吸道疾病和呼吸道外并发症，包括急性弛缓性脊髓炎。EV-D68 的全身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 如何全身传播（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一种机制。因此，我们研究了不同 EV-D68 分离株对人原代免疫细胞的易感性和容纳性。在接种 EV-D68 的人外周血单核细胞中，只有 B 细胞易感，但病毒复制受到限制。然而，在富含 B 细胞的培养物中，如 EBV 转化的 B 淋巴细胞白血病细胞系（BLCL）和原代慢病毒转导的 B 细胞，病毒能够进行复制。随后，我们表明树突状细胞（DC），特别是未成熟的 DC，对 EV-D68 感染具有易感性和容纳性，并且可以将 EV-D68 传播给自身的 BLCL。总之，我们的研究结果表明，免疫细胞，特别是 B 细胞和 DC，可能在 EV-D68 感染的发病机制中发挥重要作用。这些细胞的感染可能有助于 EV-D68 的全身传播，这是发生呼吸道外并发症的重要步骤。
肠道病毒 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发了暴发。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，包括类似脊髓灰质炎的瘫痪。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 的呼吸道外传播中发挥作用。我们表明，EV-D68 可以感染和复制特定的免疫细胞，即 B 细胞和树突状细胞（DC），并且病毒可以从 DC 转移到 B 细胞。我们的数据揭示了免疫细胞在 EV-D68 感染发病机制中的潜在作用。因此，防止 EV-D68 感染免疫细胞的干预策略可能会阻止病毒的全身传播，从而预防严重的呼吸道外并发症。
