Herpes Simplex Virus 1 (HSV-1) Infected Cell Protein 0 (ICP0) Targets of Ubiquitination during Productive Infection of Primary Adult Sensory Neurons.
Herpes Simplex Virus 1 (HSV-1) Infected Cell Protein 0 (ICP0) Targets of Ubiquitination during Productive Infection of Primary Adult Sensory Neurons.
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DOI：
10.3390/ijms24032931
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发表时间：
2023-02-02
影响因子：
5.6
通讯作者：
Bertke, Andrea S.
中科院分区：
文献类型：
--
作者：
Harrell, Telvin L.;Davido, David J.;Bertke, Andrea S.
关键词：
单纯疱疹病毒1型（HSV-1）进入感觉神经元，具有潜在的生产性或潜伏性感染。对于这两种结果，HSV-1必须减少内在免疫反应，调节病毒基因表达，并清除可能限制病毒过程的宿主蛋白质。感染细胞蛋白0（ICP 0）是一种病毒编码的E3泛素连接酶，通过介导泛素转移到靶蛋白以改变其位置、改变其功能或诱导其降解来支持这些过程。为了鉴定在感觉神经元中产生性感染期间ICP 0的泛素化靶点，我们免疫沉淀了来自HSV-1科斯感染的原代成年感觉神经元的泛素化蛋白（野生型），HSV-1 n212（表达截短的缺陷型ICP 0）和未感染的对照，使用抗泛素抗体FK 2（识别K29、K48、K63和单泛素化蛋白），然后进行LC-MS/MS和比较分析。我们鉴定了40种独特的蛋白质被ICP 0泛素化，17种蛋白质被ICP 0和宿主机制泛素化，其中高迁移率族蛋白I/Y（HMG I/Y）和TAR DNA结合蛋白43（TDP 43）被选择用于进一步分析。我们发现，ICP 0泛素化HMG I/Y和TDP 43，在生产HSV-1感染期间的特定时间点改变蛋白质表达，表明ICP 0以时间依赖性方式操纵感觉神经元环境以调节神经元中的感染结果。
Herpes simplex virus 1 (HSV-1) enters sensory neurons with the potential for productive or latent infection. For either outcome, HSV-1 must curtail the intrinsic immune response, regulate viral gene expression, and remove host proteins that could restrict viral processes. Infected cell protein 0 (ICP0), a virus-encoded E3 ubiquitin ligase, supports these processes by mediating the transfer of ubiquitin to target proteins to change their location, alter their function, or induce their degradation. To identify ubiquitination targets of ICP0 during productive infection in sensory neurons, we immunoprecipitated ubiquitinated proteins from primary adult sensory neurons infected with HSV-1 KOS (wild-type), HSV-1 n212 (expressing truncated, defective ICP0), and uninfected controls using anti-ubiquitin antibody FK2 (recognizing K29, K48, K63 and monoubiquitinated proteins), followed by LC-MS/MS and comparative analyses. We identified 40 unique proteins ubiquitinated by ICP0 and 17 ubiquitinated by both ICP0 and host mechanisms, of which High Mobility Group Protein I/Y (HMG I/Y) and TAR DNA Binding Protein 43 (TDP43) were selected for further analysis. We show that ICP0 ubiquitinates HMG I/Y and TDP43, altering protein expression at specific time points during productive HSV-1 infection, demonstrating that ICP0 manipulates the sensory neuronal environment in a time-dependent manner to regulate infection outcome in neurons.
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