The human organism is colonized by a large number of different viruses. However, very little data are available on the role of viral communities in immunosuppressed patients who undergo transplantation of solid organs or hematopoietic stem cells. In this project, we will characterize the virome of these patients who are at high risk of reactivation of many latent infections and at risk of newly acquired viral infections. The project will focus on anelloviruses and their possible role in the prediction of transplant rejection and graft versus host disease. An understanding the variability and interaction of the anelloviruses with the human immune system can help reveal their role in the immune response after transplantation. The principal investigator Ruth Tachezy and her team have experience in the characterization of clinical samples by next-generation sequencing and virome analysis.

Virus-induced tumours represent almost one tenth of human tumours. Human papillomaviruses are responsible for most of these carcinomas. Some approaches to cancer immunotherapy markedly improved treatment efficacy, but immunotherapy still failed in most patients. Therefore, mouse models of immune escape mechanisms will be developed and utilized to overcome immune evasion. In these models, cancer immunotherapy will be optimized for the induction of both innate and adaptive immune reactions that will be investigated in the tumour microenvironment. Furthermore, immunotherapy will also address immunosuppression in tumours induced with human papillomaviruses. The proposed combined cancer immunotherapy, in association with the immunoprofiling of tumour samples, could improve the individualization of cancer treatment, resulting in its enhancement. The principal investigator Ruth Tachezy and her team focus on the development of mouse tumour models with immune escape mechanisms and the characterization of immune cells in tumour microenvironment.

The molecular mechanisms how DNA viruses modulate IFN responses to their genomes are still poorly understood. Our lab recently revealed that murine polyomavirus (MPyV) induces the activation of IFN pathways via DNA sensors, p204 (human IFI16) and cGAS. The IFN response to MPyV was moderate, suggesting a strong modulation of IFN pathways by the virus. We aim to extend our studies of IFN induction pathways to the human BK Polyomavirus (BKPyV) and to uncover the mechanisms of modulation of the pathways in MPyV and BKPyV infected cells. The research will be beneficial for the treatment of human polyomaviruses and will contribute to revealing connection of IFN induction pathway with and their modulation during carcinogenesis and virus persistence. Principal investigator Sandra Huerfano’s expertise includes molecular and cellular biology of polyomaviruses and antiviral innate immunity.

Human A-to-I RNA editing enzyme ADAR1 is inducible by interferon and constitutes part of the cellular innate immunity and antiviral defence machinery. ADAR1 detailed function in viral infection can differ from virus to virus and is poorly understood. Furthermore, reduced ADAR1 activity can cause onset of type I interferonopathies such as Aicardi–Goutières Syndrome that is characterized by childhood severe encephalopathy and high mortality. We will investigate into the ADAR1 regulon with the aim to better understand its role during viral infection and to either establish ADAR1 as an emerging target for new broad-range antivirals or to identify novel cellular and viral-specific targets. Principal investigator Martin Pospíšek’s expertise includes analysis of transcriptome, translatome and RNA editome, generation and characterization of ADAR1 knock-out cell lines and analysis their response to viral infection.