HIV-1 Tat enhances replicative potential of human oral keratinocytes harboring HPV-16 genome
HIV-1 Tat enhances replicative potential of human oral keratinocytes harboring HPV-16 genome
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DOI：
10.3892/ijo_00000064
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发表时间：
2008-10-01
影响因子：
5.2
通讯作者：
Park, No-Hee
中科院分区：
文献类型：
--
作者：
Kim, Reuben H.;Yochim, Ji Min;Park, No-Hee
高效抗逆转录病毒治疗（HAART）通过降低病毒载量和增加CD 4（+）T细胞计数，显著降低了人类免疫缺陷病毒阳性（HIV+）患者的发病率和死亡率。随后，除了人乳头瘤病毒（HPV）相关病变外，许多HIV相关疾病的发生率已显着下降。这一观点提示免疫应答不是HPV感染的主要决定因素，HIV与HPV的直接相互作用可能参与了HPV相关的发病机制。在目前的研究中，我们调查是否艾滋病毒在HPV相关的口腔癌的发生中发挥直接作用，通过使用HIV-1反式激活蛋白（达特），这是已知的致癌特性。我们发现，HIV-1达特不仅增加了携带HPV-16型基因组（HOK-16 B）的人口腔角质形成细胞中HPV-16 E6和E7癌基因的表达，而且显著增强了细胞的体外增殖能力。此外，表达HIV-1达特的HOK-16 B细胞能够在裸鼠中诱导囊性结节，而对照HOK-16 B细胞不能在小鼠中产生结节。我们的研究结果表明，HIV可能通过达特蛋白发挥致癌刺激在HPV相关的发病机制中发挥作用。
Introducing highly active antiretroviral therapy (HAART) has significantly decreased the morbidity and mortality in human immunodeficiency virus-positive (HIV+) individuals by decreasing the viral loads and increasing the CD4(+) T-cell counts. Subsequently, the occurrence of many HIV-associated diseases has been dramatically declined except human papillomavirus (HPV)-associated lesions. Such notion suggests that immune response is not a major determinant, and that the direct interaction between HIV and HPV may be involved in the HPV-associated pathogenesis. In the current study, we investigated whether HIV plays a direct role in HPV-associated oral carcinogenesis by using HIV-1 transactivator protein (Tat), which is known to have oncogenic properties. We found that HIV-1 Tat not only increased the expression of HPV-16 E6 and E7 oncogenes in human oral keratinocytes harboring the HPV type-16 genome (HOK-16B), but also notably enhanced the proliferative capacity of the cells in vitro. Moreover, HOK-16B cells expressing HIV-1 Tat was capable of inducing cystic nodules in nude mice, while the control HOK-16B cells failed to produce nodules in the mice. Our results indicate that HIV could play a role in the HPV-associated pathogenesis by exerting oncogenic stimulus via Tat protein.