The ORF45 Protein of Kaposi's Sarcoma-Associated Herpesvirus and Its Critical Role in the Viral Life Cycle.
The ORF45 Protein of Kaposi's Sarcoma-Associated Herpesvirus and Its Critical Role in the Viral Life Cycle.
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DOI：
10.3390/v14092010
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发表时间：
2022-09-11
期刊：
影响因子：
--
通讯作者：
Papp B
中科院分区：
文献类型：
--
作者：
Atyeo N;Papp B
卡波西肉瘤相关疱疹病毒(KSHV)蛋白ORF45是一种与病毒粒子相关的被膜蛋白，是伽马疱疹病毒家族特有的。KSHV ORF45基因敲除突变体的产生及其随后的功能分析使人们能够更好地理解ORF45及其在KSHV裂解循环中的特定背景和关键作用。ORF45是一种多方面的蛋白质，在病毒生命周期的早期和晚期都会促进感染。作为一种即刻早期蛋白，ORF45在KSHV裂解再激活后数小时内表达，并通过多种机制在促进裂解周期中发挥重要作用，包括抑制宿主干扰素反应。作为一种被膜蛋白，ORF45对于正确靶向病毒衣壳进行包膜和释放是必要的，影响病毒生命周期的后期。越来越多的ORF45相互作用伙伴已被确定，其中最具代表性的是ORF45与宿主细胞外调节激酶(ERK)P90核糖体S6激酶(RSK)信号级联反应。在本文中，我们描述了ORF45的表达动力学，以及ORF45的宿主和病毒相互作用伙伴，以及这些相互作用在KSHV生物学中的意义。最后，我们讨论了ORF45同源基因在伽马疱疹病毒感染中的作用。
Kaposi’s sarcoma-associated herpesvirus (KSHV) protein ORF45 is a virion-associated tegument protein that is unique to the gammaherpesvirus family. Generation of KSHV ORF45-knockout mutants and their subsequent functional analyses have permitted a better understanding of ORF45 and its context-specific and vital role in the KSHV lytic cycle. ORF45 is a multifaceted protein that promotes infection at both the early and late phases of the viral life cycle. As an immediate-early protein, ORF45 is expressed within hours of KSHV lytic reactivation and plays an essential role in promoting the lytic cycle, using multiple mechanisms, including inhibition of the host interferon response. As a tegument protein, ORF45 is necessary for the proper targeting of the viral capsid for envelopment and release, affecting the late stage of the viral life cycle. A growing list of ORF45 interaction partners have been identified, with one of the most well-characterized being the association of ORF45 with the host extracellular-regulated kinase (ERK) p90 ribosomal s6 kinase (RSK) signaling cascade. In this review, we describe ORF45 expression kinetics, as well as the host and viral interaction partners of ORF45 and the significance of these interactions in KSHV biology. Finally, we discuss the role of ORF45 homologs in gammaherpesvirus infections.
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