Interferon-λ Activates a Differential Response in Peripheral Neurons That Is Effective against Alpha Herpesvirus Infections.
Interferon-λ Activates a Differential Response in Peripheral Neurons That Is Effective against Alpha Herpesvirus Infections.
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DOI：
10.3390/pathogens12091142
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发表时间：
2023-09-07
期刊：
影响因子：
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通讯作者：
Koyuncu OO
中科院分区：
文献类型：
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作者：
Salazar S;Luong KTY;Nua T;Koyuncu OO
α疱疹病毒（α-HV）在周围神经系统中建立终身潜伏感染之前感染宿主粘膜上皮细胞。病毒颗粒从粘膜到神经系统的最初传播以及内在免疫应答在这一屏障中的作用尚不清楚。使用在区室中培养的原代神经元，对伪狂犬病病毒（PRV）进行的先前研究已经证明，I型和II型干扰素（IFN）通过不同的机制诱导轴突中的局部抗病毒应答，导致病毒颗粒运输到神经元核的减少。一种称为III型IFN的新型干扰素已被证明在粘膜上皮细胞中对病毒感染起直接作用。然而，在α-HV感染期间，神经元内III型IFN的抗病毒作用在很大程度上是未知的。在这项研究中，我们专注于阐明III型干扰素对PRV神经元感染的抗病毒活性，我们比较了干扰素刺激的基因（ISGs）在神经元和非神经元细胞中的诱导模式。我们发现，IFN预暴露的原代神经元和成纤维细胞显着降低PRV病毒产量，虽然通过差异STAT激活和ISG诱导模式。值得注意的是，我们观察到III型IFN主要通过STAT 1激活来触发ISGs子集的表达，以诱导原代外周神经元中的抗病毒状态。
Alpha herpesviruses (α-HV) infect host mucosal epithelial cells prior to establishing a life-long latent infection in the peripheral nervous system. The initial spread of viral particles from mucosa to the nervous system and the role of intrinsic immune responses at this barrier is not well understood. Using primary neurons cultured in compartmentalized chambers, prior studies performed on Pseudorabies virus (PRV) have demonstrated that type I and type II interferons (IFNs) induce a local antiviral response in axons via distinct mechanisms leading to a reduction in viral particle transport to the neuronal nucleus. A new class of interferons known as type III IFNs has been shown to play an immediate role against viral infection in mucosal epithelial cells. However, the antiviral effects of type III IFNs within neurons during α-HV infection are largely unknown. In this study, we focused on elucidating the antiviral activity of type III IFN against PRV neuronal infection, and we compared the interferon-stimulated gene (ISGs) induction pattern in neurons to non-neuronal cells. We found that IFN pre-exposure of both primary neurons and fibroblast cells significantly reduces PRV virus yield, albeit by differential STAT activation and ISG induction patterns. Notably, we observed that type III IFNs trigger the expression of a subset of ISGs mainly through STAT1 activation to induce an antiviral state in primary peripheral neurons.
影响因子：
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作者：
Curanovic, Dusica;Ch'ng, Toh Hean;Szpara, Moriah;Enquist, Lynn
通讯作者：
Enquist, Lynn