Triple RNA-Seq Reveals Synergy in a Human Virus-Fungus Co-infection Model

Seelbinder, Bastian; Wallstabe, Julia; Marischen, Lothar; Weiss, Esther; Wurster, Sebastian; Page, Lukas; Löffler, Claudia; Bussemer, Lydia; Schmitt, Anna-Lena; Wolf, Thomas; Linde, Jörg GND; Cicin-Sain, Luka; Becker, Jennifer; Kalinke, Ulrich; Vogel, Jörg; Panagiotou, Gianni; Einsele, Hermann; Westermann, Alexander J.; Schäuble, Sascha; Loeffler, Juergen

High-throughput RNA sequencing (RNA-seq) is routinely applied to study diverse biological processes; however, when performed separately on interacting organisms, systemic noise intrinsic to RNA extraction, library preparation, and sequencing hampers the identification of cross-species interaction nodes. Here, we develop triple RNA-seq to simultaneously detect transcriptomes of monocyte-derived dendritic cells (moDCs) infected with the frequently co-occurring pulmonary pathogens Aspergillus fumigatus and human cytomegalovirus (CMV). Comparing expression patterns after co-infection with those after single infections, our data reveal synergistic effects and mutual interferences between host responses to the two pathogens. For example, CMV attenuates the fungus-mediated activation of pro-inflammatory cytokines through NF-κB (nuclear factor κB) and NFAT (nuclear factor of activated T cells) cascades, while A. fumigatus impairs viral clearance by counteracting viral nucleic acid-induced activation of type I interferon signaling. Together, the analytical power of triple RNA-seq proposes molecular hubs in the differential moDC response to fungal/viral single infection or co-infection that contribute to our understanding of the etiology and, potentially, clearance of post-transplant infections.

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Seelbinder, Bastian / Wallstabe, Julia / Marischen, Lothar / et al: Triple RNA-Seq Reveals Synergy in a Human Virus-Fungus Co-infection Model. 2020.

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