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PML-NB-dependent type I interferon memory results in a restricted form of HSV latency
EMBO Reports ( IF 6.5 ) Pub Date : 2021-07-01 , DOI: 10.15252/embr.202152547
Jon B Suzich 1 , Sean R Cuddy 2 , Hiam Baidas 1 , Sara Dochnal 1 , Eugene Ke 1 , Austin R Schinlever 1 , Aleksandra Babnis 1 , Chris Boutell 3 , Anna R Cliffe 1
Affiliation  

Herpes simplex virus (HSV) establishes latent infection in long-lived neurons. During initial infection, neurons are exposed to multiple inflammatory cytokines but the effects of immune signaling on the nature of HSV latency are unknown. We show that initial infection of primary murine neurons in the presence of type I interferon (IFN) results in a form of latency that is restricted for reactivation. We also find that the subnuclear condensates, promyelocytic leukemia nuclear bodies (PML-NBs), are absent from primary sympathetic and sensory neurons but form with type I IFN treatment and persist even when IFN signaling resolves. HSV-1 genomes colocalize with PML-NBs throughout a latent infection of neurons only when type I IFN is present during initial infection. Depletion of PML prior to or following infection does not impact the establishment latency; however, it does rescue the ability of HSV to reactivate from IFN-treated neurons. This study demonstrates that viral genomes possess a memory of the IFN response during de novo infection, which results in differential subnuclear positioning and ultimately restricts the ability of genomes to reactivate.

中文翻译:


PML-NB 依赖性 I 型干扰素记忆导致 HSV 潜伏期的受限形式



单纯疱疹病毒 (HSV) 在长寿神经元中建立潜伏感染。在初始感染期间,神经元暴露于多种炎性细胞因子,但免疫信号传导对 HSV 潜伏期性质的影响尚不清楚。我们发现,在存在 I 型干扰素 (IFN) 的情况下,原代小鼠神经元的初始感染会导致一种限制重新激活的潜伏期。我们还发现,初级交感神经元和感觉神经元中不存在亚核凝聚体,即早幼粒细胞白血病核体(PML-NB),但在 I 型 IFN 治疗中形成,并且即使在 IFN 信号传导消失后仍会持续存在。仅当初始感染期间存在 I 型 IFN 时,HSV-1 基因组才在神经元的潜伏感染过程中与 PML-NB 共定位。感染之前或之后 PML 的消耗不会影响建立潜伏期;然而,它确实挽救了 HSV 从 IFN 处理的神经元中重新激活的能力。这项研究表明,病毒基因组在从头感染过程中拥有对 IFN 反应的记忆,这会导致亚核定位的差异,并最终限制基因组重新激活的能力。
更新日期:2021-09-06
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