Patterns of Autologous and Nonautologous Interactions between Core Nuclear Egress Complex (NEC) Proteins of α-, β- and γ-Herpesviruses
Patterns of Autologous and Nonautologous Interactions between Core Nuclear Egress Complex (NEC) Proteins of α-, β- and γ-Herpesviruses
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DOI：
10.3390/v12030303
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发表时间：
2020-03-01
期刊：
影响因子：
4.7
通讯作者：
Marschall, Manfred
中科院分区：
文献类型：
--
作者：
Haege, Sigrun;Sonntag, Eric;Marschall, Manfred
核出口是α-、β-和γ-疱疹病毒共享的受调节的过程。核心核出口复合物（NEC）由人巨细胞病毒（HCMV）pUL 50、鼠巨细胞病毒（MCMV）pM 50、EB病毒（EBV）BFRF 1或水痘带状疱疹病毒（VZV）Orf 24的膜锚定蛋白同源物组成，它们分别与自体NEC伴侣pUL 53、pM 53、BFLF 2或Orf 27相互作用。它们募集额外的蛋白质导致多组分NEC的组装，协调调节病毒核质衣壳的排出。在这里，VZV，HCMV，MCMV和EBV核心NECs的功能进行了研究，通过共免疫沉淀和共聚焦成像分析。此外，重组MCMV，窝藏替换ORF M50的UL 50，进行了分析，在体外和体内。本质上，核心NEC相互作用严格限于自体NEC对，仅包括HCMV和MCMV同源物之间的一种可测量的非自体相互作用。MCMV-WT与MCMV-UL 50感染的鼠成纤维细胞的比较分析揭示了在蛋白质和基因组复制动力学水平上几乎相同的表型。在感染的BALB/c小鼠中，发现这些病毒在肺和其他器官中的病毒传播相当，因此说明功能互补。总之，我们的研究强调，疱疹病毒核心NEC蛋白的功能保守的核心NEC相互作用，这是发现病毒特异性或限制在亚家族内的互补性。
Nuclear egress is a regulated process shared by alpha-, beta- and gamma-herpesviruses. The core nuclear egress complex (NEC) is composed of the membrane-anchored protein homologs of human cytomegalovirus (HCMV) pUL50, murine cytomegalovirus (MCMV) pM50, Epstein-Barr virus (EBV) BFRF1 or varicella zoster virus (VZV) Orf24, which interact with the autologous NEC partners pUL53, pM53, BFLF2 or Orf27, respectively. Their recruitment of additional proteins leads to the assembly of a multicomponent NEC, coordinately regulating viral nucleocytoplasmic capsid egress. Here, the functionality of VZV, HCMV, MCMV and EBV core NECs was investigated by coimmunoprecipitation and confocal imaging analyses. Furthermore, a recombinant MCMV, harboring a replacement of ORF M50 by UL50, was analyzed both in vitro and in vivo. In essence, core NEC interactions were strictly limited to autologous NEC pairs and only included one measurable nonautologous interaction between the homologs of HCMV and MCMV. A comparative analysis of MCMV-WT versus MCMV-UL50-infected murine fibroblasts revealed almost identical phenotypes on the levels of protein and genomic replication kinetics. In infected BALB/c mice, virus spread to lung and other organs was found comparable between these viruses, thus stating functional complementarity. In conclusion, our study underlines that herpesviral core NEC proteins are functionally conserved regarding complementarity of core NEC interactions, which were found either virus-specific or restricted within subfamilies.