R-环是三聚体的RNA: DNA杂交体，是转录的重要生理调节因子; 然而，它们异常的形成或周转会导致基因组不稳定和DNA断裂。高危人乳头状瘤病毒（HPV）是生殖器和口咽癌的病原体，并且显示出增加的DNA断裂量。发现在维持高危HPV基因组的细胞中，R-环的水平增加了50倍，并且在体内的鳞状细胞宫颈癌中很容易检测到，但在正常细胞中无法检测到。在HPV阳性细胞中，高水平的R-环存在于病毒和细胞位点上，与控制其解决的RNase H1共存。在HPV阳性细胞中RNase H1的耗尽进一步增加了R-环的水平，导致病毒的转录和复制受阻，并降低了DNA修复基因（如FANCD2和ATR）的表达，这两者对病毒功能都是必需的。RNase H1的过表达降低了总R-环水平，导致DNA断裂减少了50%以上。此外，增加RNase H1的表达阻断了病毒的转录和复制，同时增强了先天免疫调控途径的因子的表达。这表明，维持高水平的R-环对于HPV的生命周期非常重要。发现E6病毒致癌蛋白通过抑制p53的转录活性诱导了高水平的R-环。我们的研究表明，高水平的R-环对HPV的致病机制至关重要，并且这取决于抑制p53途径。

R-loops are trimeric RNA: DNA hybrids that are important physiological regulators of transcription; however, their aberrant formation or turnover leads to genomic instability and DNA breaks. High-risk human papillomaviruses (HPV) are the causative agents of genital as well as oropharyngeal cancers and exhibit enhanced amounts of DNA breaks. The levels of R-loops were found to be increased up to 50-fold in cells that maintain high-risk HPV genomes and were readily detected in squamous cell cervical carcinomas in vivo but not in normal cells. The high levels of R-loops in HPV-positive cells were present on both viral and cellular sites together with RNase H1, an enzyme that controls their resolution. Depletion of RNase H1 in HPV-positive cells further increased R-loop levels, resulting in impaired viral transcription and replication along with reduced expression of the DNA repair genes such as FANCD2 and ATR, both of which are necessary for viral functions. Overexpression of RNase H1 decreased total R-loop levels, resulting in a reduction of DNA breaks by over 50%. Furthermore, increased RNase H1 expression blocked viral transcription and replication while enhancing the expression of factors in the innate immune regulatory pathway. This suggests that maintaining elevated R-loop levels is important for the HPV life cycle. The E6 viral oncoprotein was found to be responsible for inducing high levels of R-loops by inhibiting p53's transcriptional activity. Our studies indicate that high R-loop levels are critical for HPV pathogenesis and that this depends on suppressing the p53 pathway.