Department of Pediatrics, Research Center for Translational Medicine and Key Laboratory of Arrhythmias, East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Pediatrics, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, Louisiana, USA.
J Virol. 2018 Jun 29;92(14). doi: 10.1128/JVI.00478-18. Print 2018 Jul 15.
Kaposi's sarcoma-associated herpesvirus (KSHV) can cause several human cancers, including primary effusion lymphoma (PEL), which frequently occur in immunocompromised patients. KSHV-infected patients often suffer from polymicrobial infections caused by opportunistic bacterial pathogens. Therefore, it is crucial to understand how these coinfecting microorganisms or their secreted metabolites may affect KSHV infection and the pathogenesis of virus-associated malignancies. Quorum sensing (QS), a cell density-based intercellular communication system, employs extracellular diffusible signaling molecules to regulate bacterial virulence mechanisms in a wide range of bacterial pathogens, such as , which is one of the most common opportunistic microorganisms found in immunocompromised individuals. In this study, we evaluated and compared the influence on PEL growth and the host/viral interactome of the major QS signaling molecules [-(3-oxododecanoyl)-l-homoserine lactone (OdDHL), -butyrylhomoserine lactone (BHL), and 2-heptyl-3-hydroxy-4-quinolone (PQS)] in conditioned medium from wild-type (wt) and QS mutant laboratory strains as well as clinical isolates of Our data indicate that coinfection may facilitate virus dissemination and establishment of new infection and further promote tumor development through effectively inducing viral lytic gene expression by its QS systems. Currently, most studies about KSHV infection and/or virus-associated malignancies depend on pure culture systems or immunodeficient animal models. However, the real situation should be much more complicated in KSHV-infected immunocompromised patients due to frequent polymicrobial infections. It is important to understand the interaction of KSHV and coinfecting microorganisms, especially opportunistic bacterial pathogens. Here we report for the first time that and its quorum-sensing signaling molecules display a complicated impact on KSHV-associated lymphoma growth as well as the intracellular host/viral gene expression profile. Our data imply that targeting of coinfecting pathogens is probably necessary during treatment of virus-associated malignancies in these immunocompromised patients.
卡波西肉瘤相关疱疹病毒（KSHV）可引起几种人类癌症，包括原发性渗出性淋巴瘤（PEL），这种疾病常发生在免疫功能低下的患者中。KSHV 感染患者常患有机会性细菌病原体引起的多种微生物感染。因此，了解这些共生微生物或其分泌的代谢物如何影响 KSHV 感染和病毒相关恶性肿瘤的发病机制至关重要。群体感应（QS）是一种基于细胞密度的细胞间通讯系统，它利用细胞外可扩散的信号分子来调节多种细菌病原体中的细菌毒力机制，包括铜绿假单胞菌，这是免疫功能低下个体中最常见的机会性微生物之一。在这项研究中，我们评估并比较了来自野生型（wt）和 QS 突变实验室菌株以及临床分离株的主要 QS 信号分子[-(3-氧代十二烷酰基)-l-高丝氨酸内酯（OdDHL）、-丁酰基高丝氨酸内酯（BHL）和 2-庚基-3-羟基-4-喹诺酮（PQS）]在条件培养基中对 PEL 生长和宿主/病毒互作组的影响。我们的数据表明，铜绿假单胞菌感染可能通过其 QS 系统有效诱导病毒裂解基因表达，从而促进病毒的传播和新感染的建立，并进一步促进肿瘤的发展。目前，大多数关于 KSHV 感染和/或病毒相关恶性肿瘤的研究依赖于纯培养系统或免疫缺陷动物模型。然而，由于频繁的多种微生物感染，KSHV 感染的免疫功能低下患者的实际情况应该要复杂得多。了解 KSHV 与共生微生物，特别是机会性细菌病原体的相互作用非常重要。在这里，我们首次报道铜绿假单胞菌及其群体感应信号分子对 KSHV 相关淋巴瘤生长以及细胞内宿主/病毒基因表达谱有复杂的影响。我们的数据表明，在这些免疫功能低下的患者中治疗病毒相关恶性肿瘤时，针对共生病原体的治疗可能是必要的。
