Porphyromonas gingivalis coinfects with KSHV in oral cavities of HIV+ patients and induces viral lytic reactivation.

Kaposi’s sarcoma-associated herpesvirus (KSHV) infection causes several human cancers, including Kaposi’s sarcoma (KS), one of the most common AIDS-associated tumors. The involvement of the oral cavity represents one common clinical manifestation of AIDS-KS Individuals with periodontal diseases and an oral carriage of a variety of pathogenic bacteria, including Porphyromonas gingivalis. In the current study, we report clinical relevance of P. gingivalis and KSHV co-infection in the oral cavity of a cohort of HIV+ patients. Furthermore, we found that P. gingivalis conditioned medium or derived lipopolysaccharide (LPS) effectively induced KSHV lytic reactivation from infected oral cells. This reactivation requires TLR4 as well as the activities of p38 and JNK MAPK signaling pathways. Our findings reveal the mechanisms through which co-infected periodontal pathogens potentially promote oncogenic virus pathogenesis in the unique niche of immunocompromised patients.

卡波西肉瘤相关疱疹病毒（KSHV）感染导致多种人类癌症，包括卡波西肉瘤（KS），它是最常见的艾滋病相关肿瘤之一。口腔受累是艾滋病相关卡波西肉瘤的一种常见临床表现。患有牙周疾病且口腔携带多种病原菌（包括牙龈卟啉单胞菌）的个体。在当前的研究中，我们报道了在一组艾滋病病毒（HIV）阳性患者的口腔中牙龈卟啉单胞菌和KSHV共同感染的临床相关性。此外，我们发现牙龈卟啉单胞菌条件培养基或其衍生的脂多糖（LPS）能有效地诱导感染的口腔细胞中KSHV的裂解性再激活。这种再激活需要Toll样受体4（TLR4）以及p38和JNK丝裂原活化蛋白激酶（MAPK）信号通路的活性。我们的研究结果揭示了共同感染的牙周病原菌在免疫功能低下患者的独特微环境中潜在促进致癌病毒发病机制的途径。