KSHV co-infection down-regulates HPV16 E6 and E7 from cervical cancer cells.
KSHV co-infection down-regulates HPV16 E6 and E7 from cervical cancer cells.
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KSHV 联合感染下调宫颈癌细胞中的 HPV16 E6 和 E7
DOI：
10.18632/oncotarget.16207
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发表时间：
2017-05-30
期刊：
影响因子：
--
通讯作者：
Qin Z
中科院分区：
文献类型：
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作者：
Dai L;Cao Y;Jiang W;Zabaleta J;Liu Z;Qiao J;Qin Z
高危人乳头瘤病毒（HPV）感染是一些恶性肿瘤的病因，如宫颈癌、口腔癌和口咽癌。卡波西肉瘤相关疱疹病毒（KSHV）是免疫功能低下患者中几种人类癌症的主要病原体。有趣的是，KSHV DNA已在口腔和女性生殖道中检测到，尽管其在宫颈样本中的检出率非常低，很少有关于KSHV/HPV合并感染的报道。因此，目前尚不清楚KSHV合并感染在hpv相关肿瘤发生中的作用。在本研究中，我们报道了hpv16整合子宫颈癌细胞系SiHa易受KSHV潜伏感染和复制。我们还发现KSHV感染或病毒潜伏蛋白能够通过操纵细胞microRNA功能来降低hpv16e6 /E7的表达。阵列分析表明，KSHV感染诱导了部分炎性细胞因子/趋化因子的产生，并上调了一系列干扰素诱导的基因表达，这可能有助于宿主免疫防御系统攻击这些共感染细胞并清除病毒。总之，我们的数据为宫颈样本和/或宫颈癌细胞中KSHV脱落和KSHV/HPV合并感染的低检出率提供了可能的解释。
High-risk human papillomavirus (HPV) infection is the etiological agent of some malignancies such as cervical, oral and oropharyngeal cancers. Kaposi sarcoma-associated herpesvirus (KSHV) represents a principal causative agent of several human cancers arising in those immunocompromised patients. Interestingly, KSHV DNA has been detected in the oral cavity and the female genital tract, although its detection rate in cervical samples is very low and few reports are about KSHV/HPV co-infection. Therefore, it remains unclear about the role of KSHV co-infection in the development of HPV-related neoplasias. In the current study, we report that HPV16-integrated cervical cancer cell-line SiHa is susceptible to KSHV latent infection and replication. We also have found that KSHV infection or viral latent proteins are capable of reducing HPV16 E6/E7 expression through the manipulation of cellular microRNA function. Array analysis indicates that KSHV infection induces some inflammatory cytokines/chemokines production as well as up-regulates a series of interferon-induced genes expression, which may facilitate host immune defense system attacking these co-infected cells and clearance of viruses. Together, our data have provided possible explanations for very low detection rate of KSHV shedding as well as of KSHV/HPV co-infection in cervical samples and/or cervical cancer cells.