模拟寨卡病毒感染期间的神经免疫相互作用。
Modeling neuro-immune interactions during Zika virus infection.
机构信息
Department of Pediatrics/Rady Children's Hospital San Diego, University of California San Diego, La Jolla, CA 92093-0695, USA.
Department of Cellular & Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego, La Jolla, CA 92093-0695, USA.
出版信息
Hum Mol Genet. 2018 Jan 1;27(1):41-52. doi: 10.1093/hmg/ddx382.
Although Zika virus (ZIKV) infection is often asymptomatic, in some cases, it can lead to birth defects in newborns or serious neurologic complications in adults. However, little is known about the interplay between immune and neural cells that could contribute to the ZIKV pathology. To understand the mechanisms at play during infection and the antiviral immune response, we focused on neural precursor cells (NPCs)-microglia interactions. Our data indicate that human microglia infected with the current circulating Brazilian ZIKV induces a similar pro-inflammatory response found in ZIKV-infected human tissues. Importantly, using our model, we show that microglia interact with ZIKV-infected NPCs and further spread the virus. Finally, we show that Sofosbuvir, an FDA-approved drug for Hepatitis C, blocked viral infection in NPCs and therefore the transmission of the virus from microglia to NPCs. Thus, our model provides a new tool for studying neuro-immune interactions and a platform to test new therapeutic drugs.
虽然 Zika 病毒（ZIKV）感染通常无症状，但在某些情况下，它可导致新生儿出生缺陷或成年人严重的神经并发症。然而，人们对可能导致 ZIKV 病理学的免疫细胞和神经细胞之间的相互作用知之甚少。为了了解感染过程中和抗病毒免疫反应中的机制，我们专注于神经前体细胞（NPC）-小胶质细胞相互作用。我们的数据表明，感染当前流行的巴西 ZIKV 的人源小胶质细胞诱导出与在 ZIKV 感染的人组织中发现的相似的促炎反应。重要的是，我们使用该模型表明小胶质细胞与 ZIKV 感染的 NPC 相互作用，并进一步传播病毒。最后，我们表明 Sofosbuvir（一种批准用于治疗丙型肝炎的 FDA 药物）可阻断 NPC 中的病毒感染，从而阻止病毒从小胶质细胞传播到 NPC。因此，我们的模型为研究神经免疫相互作用提供了新工具，并为测试新的治疗药物提供了平台。
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