Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Laboratory of Immunobiology, Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, Santa Catarina 88040-900, Brazil.
Viruses. 2017 Nov 16;9(11):342. doi: 10.3390/v9110342.
Herpes simplex virus 1 (HSV-1) has extensive interactions with the host DNA damage response (DDR) machinery that can be either detrimental or beneficial to the virus. Proteins in the homologous recombination pathway are known to be required for efficient replication of the viral genome, while different members of the classical non-homologous end-joining (c-NHEJ) pathway have opposing effects on HSV-1 infection. Here, we have investigated the role of the recently-discovered c-NHEJ component, PAXX (Paralogue of XRCC4 and XLF), which we found to be excluded from the nucleus during HSV-1 infection. We have established that cells lacking PAXX have an intact innate immune response to HSV-1 but show a defect in viral genome replication efficiency. Counterintuitively, cells were able to produce greater numbers of infectious virions, indicating that PAXX acts to restrict HSV-1 infection in a manner that is different from other c-NHEJ factors.
单纯疱疹病毒 1（HSV-1）与宿主 DNA 损伤反应（DDR）机制有广泛的相互作用，这些相互作用对病毒可能有害也可能有益。同源重组途径中的蛋白质已知是病毒基因组有效复制所必需的，而经典非同源末端连接（c-NHEJ）途径的不同成员对 HSV-1 感染有相反的影响。在这里，我们研究了最近发现的 c-NHEJ 成分 PAXX（XRCC4 和 XLF 的同源物）的作用，我们发现它在 HSV-1 感染期间被排除在核外。我们已经确定，缺乏 PAXX 的细胞对 HSV-1 有完整的先天免疫反应，但病毒基因组复制效率存在缺陷。与直觉相反的是，细胞能够产生更多数量的感染性病毒粒子，这表明 PAXX 以不同于其他 c-NHEJ 因子的方式限制 HSV-1 感染。
