Division of Biology, Kansas State University, Manhattan, KS 66506, USA.
Viruses. 2022 Apr 30;14(5):948. doi: 10.3390/v14050948.
Beta human papillomavirus (beta HPV) infections are common in adults. Certain types of beta HPVs are associated with nonmelanoma skin cancer (NMSC) in immunocompromised individuals. However, whether beta HPV infections promote NMSC in the immunocompetent population is unclear. They have been hypothesized to increase genomic instability stemming from ultraviolet light exposure by disrupting DNA damage responses. Implicit in this hypothesis is that the virus encodes one or more proteins that impair DNA repair signaling. Fluorescence-based reporters, next-generation sequencing, and animal models have been used to test this primarily in cells expressing beta HPV E6/E7. Of the two, beta HPV E6 appears to have the greatest ability to increase UV mutagenesis, by attenuating two major double-strand break (DSB) repair pathways, homologous recombination, and non-homologous end-joining. Here, we review this dysregulation of DSB repair and emerging approaches that can be used to further these efforts.
β型人乳头瘤病毒（β HPV）感染在成年人中很常见。某些类型的β HPV 与免疫功能低下个体的非黑色素瘤皮肤癌（NMSC）有关。然而，β HPV 感染是否会促进免疫功能正常人群的 NMSC 尚不清楚。人们假设，通过破坏 DNA 损伤反应，β HPV 会增加由紫外线照射引起的基因组不稳定性。这一假设的隐含前提是，该病毒编码一种或多种蛋白，削弱 DNA 修复信号。荧光报告基因、下一代测序和动物模型已被用于主要在表达β HPV E6/E7 的细胞中对此进行测试。在这两种蛋白中，β HPV E6 似乎通过削弱两条主要的双链断裂（DSB）修复途径——同源重组和非同源末端连接，具有最大的增加 UV 诱变的能力。在这里，我们回顾了 DSB 修复的这种失调以及可以用于进一步推进这些研究的新兴方法。
