The Carboxyl Terminus of Tegument Protein pUL21 Contributes to Pseudorabies Virus Neuroinvasion
The Carboxyl Terminus of Tegument Protein pUL21 Contributes to Pseudorabies Virus Neuroinvasion
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外皮蛋白 pUL21 的羧基末端有助于伪狂犬病病毒神经侵袭
DOI：
10.1128/jvi.02052-18
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发表时间：
2019-01
影响因子：
5.4
通讯作者：
Liu Zheng-Fei
中科院分区：
文献类型：
--
作者：
Yan Kai;Liu Jie;Guan Xiang;Yin Yi-Xin;Peng Hui;Chen Huan-Chun;Liu Zheng-Fei
疱疹病毒是一组感染人类和动物的DNA病毒。α疱疹病毒的特征在于其在外周神经元中建立潜伏感染的能力。进入神经元后，疱疹病毒衣壳与细胞运动蛋白相互作用，并在轴突微管上进行逆行转运。这个复杂的过程对疱疹病毒的生命周期至关重要，但其潜在机制仍然知之甚少。在这里，我们确定pUL 21是伪狂犬病病毒（PRV）的内层蛋白，它与细胞质动力蛋白轻链路障-1相互作用。我们还观察到pUL 21促进PRV在神经细胞中的逆行转运。此外，我们的研究结果证实，pUL 21有助于PRV在体内的神经侵袭。重要的是，pUL 21的羧基末端负责与Roadblock-1相互作用，并且该结构域有助于PRV的神经侵袭。这项研究为α疱疹病毒的神经侵袭和PRV感染过程中病毒与宿主之间的相互作用提供了新的见解。伪狂犬病病毒（PRV）进入细胞后，利用微管将其核衣壳运送到细胞核。先前的研究表明PRV VP 1/2是动力蛋白介导的衣壳转运的效应子。然而，PRV招募微管马达蛋白成功的神经侵袭和神经毒力的机制还没有很好的理解。在这里，我们提供的证据表明，PRV pUL 21是一个内层蛋白。我们使用双分子荧光互补（BiFC）测定测试了其与细胞质轻链的相互作用，并观察到PRV pUL 21与Roadblock-1相互作用。这种相互作用通过免疫共沉淀（co-IP）试验证实。我们还确定了使用微流控室系统的PRV株的逆行和顺行轴突运输的效率，并研究了pUL 21的体内PRV神经侵袭的贡献。进一步的数据表明，pUL 21的羧基端是必不可少的，它与路障-1的相互作用，这一领域有助于PRV逆行轴突运输在体外和体内。我们的研究结果表明，羧基末端pUL 21有助于PRV的神经侵袭。疱疹病毒是一组DNA病毒，感染人类和动物。α疱疹病毒的特点是能够在外周神经元中建立潜伏感染。进入神经元后，疱疹病毒衣壳与细胞运动蛋白相互作用，并在轴突微管上进行逆行转运。这个复杂的过程对疱疹病毒的生命周期至关重要，但其潜在机制仍然知之甚少。在这里，我们确定pUL 21是伪狂犬病病毒（PRV）的内层蛋白，它与细胞质动力蛋白轻链路障-1相互作用。我们还观察到pUL 21促进PRV在神经细胞中的逆行转运。此外，我们的研究结果证实，pUL 21有助于PRV在体内的神经侵袭。重要的是，pUL 21的羧基末端负责与Roadblock-1相互作用，并且该结构域有助于PRV神经侵袭。这项研究为α疱疹病毒的神经侵袭和PRV感染过程中病毒与宿主之间的相互作用提供了新的见解。
Herpesviruses are a group of DNA viruses that infect both humans and animals. Alphaherpesviruses are distinguished by their ability to establish latent infection in peripheral neurons. After entering neurons, the herpesvirus capsid interacts with cellular motor proteins and undergoes retrograde transport on axon microtubules. This elaborate process is vital to the herpesvirus lifecycle, but the underlying mechanism remains poorly understood. Here, we determined that pUL21 is an inner tegument protein of pseudorabies virus (PRV) and that it interacts with the cytoplasmic dynein light chain Roadblock-1. We also observed that pUL21 promotes retrograde transport of PRV in neuronal cells. Furthermore, our findings confirm that pUL21 contributes to PRV neuroinvasion in vivo. Importantly, the carboxyl terminus of pUL21 is responsible for interaction with Roadblock-1, and this domain contributes to PRV neuroinvasion. This study offers fresh insights into alphaherpesvirus neuroinvasion and the interaction between virus and host during PRV infection. ABSTRACT Following its entry into cells, pseudorabies virus (PRV) utilizes microtubules to deliver its nucleocapsid to the nucleus. Previous studies have shown that PRV VP1/2 is an effector of dynein-mediated capsid transport. However, the mechanism of PRV for recruiting microtubule motor proteins for successful neuroinvasion and neurovirulence is not well understood. Here, we provide evidence that PRV pUL21 is an inner tegument protein. We tested its interaction with the cytoplasmic light chains using a bimolecular fluorescence complementation (BiFC) assay and observed that PRV pUL21 interacts with Roadblock-1. This interaction was confirmed by coimmunoprecipitation (co-IP) assays. We also determined the efficiency of retrograde and anterograde axonal transport of PRV strains in explanted neurons using a microfluidic chamber system and investigated pUL21’s contribution to PRV neuroinvasion in vivo. Further data showed that the carboxyl terminus of pUL21 is essential for its interaction with Roadblock-1, and this domain contributes to PRV retrograde axonal transport in vitro and in vivo. Our findings suggest that the carboxyl terminus of pUL21 contributes to PRV neuroinvasion. IMPORTANCE Herpesviruses are a group of DNA viruses that infect both humans and animals. Alphaherpesviruses are distinguished by their ability to establish latent infection in peripheral neurons. After entering neurons, the herpesvirus capsid interacts with cellular motor proteins and undergoes retrograde transport on axon microtubules. This elaborate process is vital to the herpesvirus lifecycle, but the underlying mechanism remains poorly understood. Here, we determined that pUL21 is an inner tegument protein of pseudorabies virus (PRV) and that it interacts with the cytoplasmic dynein light chain Roadblock-1. We also observed that pUL21 promotes retrograde transport of PRV in neuronal cells. Furthermore, our findings confirm that pUL21 contributes to PRV neuroinvasion in vivo. Importantly, the carboxyl terminus of pUL21 is responsible for interaction with Roadblock-1, and this domain contributes to PRV neuroinvasion. This study offers fresh insights into alphaherpesvirus neuroinvasion and the interaction between virus and host during PRV infection.
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影响因子：
4.8
作者：
Hernandez, Felicia P.;Sandri-Goldin, Rozanne M.
通讯作者：
Sandri-Goldin, Rozanne M.
影响因子：
5.6
作者：
Jikui Song;R. Tyler;Min S. Lee;Ejan M. Tyler;J. Markley
通讯作者：
Jikui Song;R. Tyler;Min S. Lee;Ejan M. Tyler;J. Markley
影响因子：
3.5
作者：
Jiang, JM;Yu, L;Zhao, SY
通讯作者：
Zhao, SY
影响因子：
5.4
作者：
Curanovic, D.;Lyman, M. G.;Enquist, L. W.
通讯作者：
Enquist, L. W.
DOI：
10.1073/pnas.0707452104
发表时间：
2007-11-20
影响因子：
11.1
作者：
Atanasiu, Doina;Whitbeck, J. Charles;Eisenberg, Roselyn J.
通讯作者：
Eisenberg, Roselyn J.