Lipoteichoic Acid (LTA) and Lipopolysaccharides (LPS) from Periodontal Pathogenic Bacteria Facilitate Oncogenic Herpesvirus Infection within Primary Oral Cells
Lipoteichoic Acid (LTA) and Lipopolysaccharides (LPS) from Periodontal Pathogenic Bacteria Facilitate Oncogenic Herpesvirus Infection within Primary Oral Cells
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牙周病原菌中的脂磷壁酸 (LTA) 和脂多糖 (LPS) 促进原代口腔细胞内的致癌疱疹病毒感染
DOI：
10.1371/journal.pone.0101326
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发表时间：
2014-06-27
期刊：
影响因子：
3.7
通讯作者：
Qin, Zhiqiang
中科院分区：
文献类型：
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作者：
Dai, Lu;Defee, Michael R.;Qin, Zhiqiang
卡波西肉瘤（KS）仍然是HIV/AIDS患者中最常见的肿瘤，口腔受累是这种肿瘤最常见的临床表现之一。艾滋病毒感染会增加患牙周病和口腔携带各种细菌的风险。在局部环境中致病菌和致癌病毒的相互作用是否促进了这些病毒在口腔中的复制或维持仍然是未知的。在目前的研究中，我们的数据表明，预处理的原代人口腔成纤维细胞与两个典型的病原体相关的分子模式（PAMPs）产生的口腔致病菌-脂磷壁酸（LTA）和脂多糖（LPS），增加KSHV的进入和随后的病毒潜伏基因的表达在从头感染。进一步的实验表明，LTA和/或LPS诱导的潜在机制包括上调细胞受体，增加活性氧（ROS）的产生，以及激活细胞内信号通路如MAPK和NF-κ B，并且所有这些都与口腔细胞内的KSHV进入或基因表达密切相关。基于这些发现，我们希望提供开发新的靶向方法的框架，用于治疗和预防高危HIV阳性患者的口腔KSHV感染和KS发展。
Kaposi's sarcoma (KS) remains the most common tumor arising in patients with HIV/AIDS, and involvement of the oral cavity represents one of the most common clinical manifestations of this tumor. HIV infection incurs an increased risk for periodontal diseases and oral carriage of a variety of bacteria. Whether interactions involving pathogenic bacteria and oncogenic viruses in the local environment facilitate replication or maintenance of these viruses in the oral cavity remains unknown. In the current study, our data indicate that pretreatment of primary human oral fibroblasts with two prototypical pathogen-associated molecular patterns (PAMPs) produced by oral pathogenic bacteria-lipoteichoic acid (LTA) and lipopolysaccharide (LPS), increase KSHV entry and subsequent viral latent gene expression during de novo infection. Further experiments demonstrate that the underlying mechanisms induced by LTA and/or LPS include upregulation of cellular receptor, increasing production of reactive oxygen species (ROS), and activating intracellular signaling pathways such as MAPK and NF-kappa B, and all of which are closely associated with KSHV entry or gene expression within oral cells. Based on these findings, we hope to provide the framework of developing novel targeted approaches for treatment and prevention of oral KSHV infection and KS development in high-risk HIV-positive patients.