Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611, USA.
Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611, USA.
Virology. 2020 Aug;547:27-34. doi: 10.1016/j.virol.2020.05.003. Epub 2020 May 22.
The mechanisms regulating viral pathogenesis of human papillomavirus (HPV) associated oropharyngeal squamous cell cancers (OPSCC) are not well understood. In the cervix, activation of DNA damage repair pathways is critical for viral replication but little is known about their role in OPSCC. APOBEC factors have been shown to be increased in OPSCC but the significance of this is unclear. We therefore examined activation of DNA damage and APOBEC factors in HPV-induced OPSCC. Our studies show significantly increased levels of pCHK1, FANCD2, BRCA1, RAD51, pSMC1 and γH2AX foci in HPV-positive samples as compared to HPV-negative while the ATM effector kinase, pCHK2, was not increased. Similar differences were observed when the levels of proteins were examined in OPSCC cell lines. In contrast, the levels of APOBEC3B and 3A were found to be similar in both HPV-positive and -negative OPSCC. Our studies suggest members of ATR pathway and FANCD2 may be important in HPV-induced OPSCC.
人乳头瘤病毒（HPV）相关口咽鳞状细胞癌（OPSCC）的发病机制的调节机制尚不清楚。在宫颈中，DNA 损伤修复途径的激活对于病毒复制至关重要，但对于其在 OPSCC 中的作用知之甚少。已表明 APOBEC 因子在 OPSCC 中增加，但这一意义尚不清楚。因此，我们研究了 HPV 诱导的 OPSCC 中 DNA 损伤和 APOBEC 因子的激活情况。我们的研究表明，与 HPV 阴性样本相比，HPV 阳性样本中 pCHK1、FANCD2、BRCA1、RAD51、pSMC1 和 γH2AX 焦点的水平显著增加，而 ATM 效应激酶 pCHK2 没有增加。在 OPSCC 细胞系中检查蛋白水平时观察到类似的差异。相比之下，在 HPV 阳性和阴性 OPSCC 中发现 APOBEC3B 和 3A 的水平相似。我们的研究表明，ATR 途径和 FANCD2 的成员可能在 HPV 诱导的 OPSCC 中很重要。
