Regulation of Virus-Associated Lymphoma Growth and Gene Expression by Bacterial Quorum-Sensing Molecules.
Regulation of Virus-Associated Lymphoma Growth and Gene Expression by Bacterial Quorum-Sensing Molecules.
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细菌群体感应分子对病毒相关淋巴瘤生长和基因表达的调节
DOI：
10.1128/jvi.00478-18
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发表时间：
2018
影响因子：
5.4
通讯作者：
Qin Zhiqiang
中科院分区：
文献类型：
--
作者：
Qiao Jing;Cao Yueyu;Zabaleta Jovanny;Yang Liang;Dai Lu;Qin Zhiqiang
卡波西肉瘤相关疱疹病毒（KSHV）可引起多种人类癌症，包括原发性渗出性淋巴瘤（PEL），常发生于免疫功能低下的患者。KSHV感染的患者通常患有由机会性细菌病原体引起的多种微生物感染。因此，了解这些共同感染的微生物或其分泌的代谢产物如何影响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（Quorum sensing，QS）是一种基于细胞密度的细胞间通讯系统，利用细胞外可扩散的信号分子来调节广泛的细菌病原体中的细菌毒力机制，例如铜绿假单胞菌，其是在免疫功能低下个体中发现的最常见的机会微生物之一。在本研究中，我们评估并比较了铜绿假单胞菌野生型（wt）和QS突变实验室菌株以及临床分离株的条件培养基中主要QS信号分子[N-（3-氧代十二烷酰基）-l-高丝氨酸内酯（OdDHL）、N-丁酰高丝氨酸内酯（BHL）和2-庚基-3-羟基-4-喹诺酮（PQS）]对PEL生长和宿主/病毒相互作用组的影响。我们的数据表明，铜绿假单胞菌合并感染可能有助于病毒传播和建立新的感染，并通过其QS系统有效地诱导病毒裂解基因的表达，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，真实的情况应该是复杂得多的KSHV感染的免疫功能低下的患者，由于频繁的多种微生物感染。了解KSHV与共感染微生物，特别是条件致病菌的相互作用是很重要的。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/病毒基因表达谱表现出复杂的影响。我们的数据表明，在这些免疫功能低下的患者中，在病毒相关恶性肿瘤的治疗过程中，靶向共感染病原体可能是必要的。
ABSTRACT 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 Pseudomonas aeruginosa, 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 [N-(3-oxododecanoyl)-l-homoserine lactone (OdDHL), N-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 P. aeruginosa. Our data indicate that P. aeruginosa 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. IMPORTANCE 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 P. aeruginosa 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.