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脊髓灰质炎病毒 1 型野毒株和萨宾减毒株在人神经细胞中诱导 Toll 样受体和 1 型干扰素的差异。

Differential induction of Toll-like receptors & type 1 interferons by Sabin attenuated & wild type 1 polioviruses in human neuronal cells.

机构信息

Enterovirus Research Centre (ICMR), Mumbai, India.

出版信息

Indian J Med Res. 2013;138(2):209-18.

PMID:24056597
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3788206/
Abstract

BACKGROUND & OBJECTIVES: Polioviruses are the causative agent of paralytic poliomyelitis. Attenuated polioviruses (Sabin oral poliovirus vaccine strains) do not replicate efficiently in neurons as compared to the wild type polioviruses and therefore do not cause disease. This study was aimed to investigate the differential host immune response to wild type 1 poliovirus (wild PV) and Sabin attenuated type 1 poliovirus (Sabin PV) in cultured human neuronal cells.

METHODS

By using flow cytometry and real time PCR methods we examined host innate immune responses and compared the role of toll like receptors (TLRs) and cytoplasmic RNA helicases in cultured human neuronal cells (SK-N-SH) infected with Sabin PV and wild PV.

RESULTS

Human neuronal cells expressed very low levels of TLRs constitutively. Sabin PV infection induced significantly higher expression of TLR3, TLR7 and melanoma differentiation-associated protein-5 (MDA-5) m-RNA in neuronal cells at the beginning of infection (up to 4 h) as compared to wild PV. Further, Sabin PV also induced the expression of interferon α/β at early time point of infection. The induced expression of IFN α/β gene by Sabin PV in neuronal cells could be suppressed by inhibiting TLR7.

INTERPRETATION & CONCLUSIONS: Neuronal cell innate immune response to Sabin and wild polioviruses differ significantly for TLR3, TLR7, MDA5 and type 1 interferons. Effects of TLR7 activation and interferon production and Sabin virus replication in neuronal cells need to be actively investigated in future studies.

摘要

背景与目的

脊髓灰质炎病毒是引起麻痹性脊髓灰质炎的病原体。与野生型脊髓灰质炎病毒相比，减毒脊髓灰质炎病毒（Sabin 口服脊髓灰质炎疫苗株）在神经元中不能有效复制，因此不会引起疾病。本研究旨在探讨野生型 1 型脊髓灰质炎病毒（野生 PV）和 Sabin 减毒 1 型脊髓灰质炎病毒（Sabin PV）在培养的人神经元细胞中引起的宿主免疫反应的差异。

方法

通过流式细胞术和实时 PCR 方法，我们检测了宿主固有免疫反应，并比较了 Toll 样受体（TLRs）和细胞质 RNA 解旋酶在 Sabin PV 和野生 PV 感染培养的人神经元细胞（SK-N-SH）中的作用。

结果

人神经元细胞持续表达低水平的 TLRs。与野生 PV 相比，Sabin PV 感染在感染初期（高达 4 小时）诱导神经元细胞中 TLR3、TLR7 和黑色素瘤分化相关蛋白 5（MDA-5）mRNA 的表达显著升高。此外，Sabin PV 还在感染的早期诱导干扰素 α/β的表达。Sabin PV 在神经元细胞中诱导 IFNα/β基因的表达可以通过抑制 TLR7 来抑制。

解释与结论

神经元细胞对 Sabin 和野生脊髓灰质炎病毒的固有免疫反应在 TLR3、TLR7、MDA5 和 I 型干扰素方面存在显著差异。需要在未来的研究中积极研究 TLR7 激活和干扰素产生以及 Sabin 病毒在神经元细胞中的复制的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c761/3788206/853a8620daaf/IJMR-138-209-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c761/3788206/853a8620daaf/IJMR-138-209-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c761/3788206/7328b550b7c0/IJMR-138-209-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c761/3788206/20f198591454/IJMR-138-209-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c761/3788206/3e9dfb09d336/IJMR-138-209-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c761/3788206/e18b06fc683b/IJMR-138-209-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c761/3788206/853a8620daaf/IJMR-138-209-g009.jpg

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