Regulation of virus-associated lymphoma growth and gene expression by bacterial quorum sensing molecules
Reference: Journal of Virology (2018) 92: e00478-00418.

Kaposi 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 co-infected microorganisms or their secreted metabolites may affect KSHV infection and virus-associated malignancies pathogenesis. 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 mostly common opportunistic microorganisms found in immunocompromised individuals. In this study, we evaluated and compared the influence of PEL growth and host/viral interactome by the major QS signal molecules (OdDHL, BHL and PQS), the conditioned medium from wild type (wt) and QS mutants of laboratory strains as well as clinical isolates of P. aeruginosa. Our data indicate that P. aeruginosa co-infection may facilitate virus dissemination, 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 system or immunodeficiency 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 co-infected microorganisms, especially those opportunistic bacterial pathogens. Here we for the first time report that P. aeruginosa and its quorum sensing signaling molecules display a complicated impact on KSHV-associated lymphoma growth as well as intracellular host/viral gene expression profile. Our data imply that targeting co-infected pathogens is probably necessary when treatment of virus-associated malignancies in these immunocompromised patients.

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Qiao J., Cao Y., Zabaleta J., Yang L., Dai L., Qin Z.