To date, despite a vast range of classical and molecular diagnostic tools, the etiology of many, presumed viral infections still remains undetermined. This is especially the case for diarrhea, encephalitis and respiratory tract infections. While definition of mildly pathogenic or apathogenic viral infections is often not of clinical importance, it can be vital in immune compromised individuals.
Next Generation Sequencing (NGS) combined with virus sequence-independent amplification by random PCR allows for unbiased and massive parallel sequencing of total viral nucleic acids. Using this methodology, the virus profile or viral metagenome can be obtained, identifying all virus species and their relative abundances in a given sample. This approach offers therefore unprecedented possibilities for characterization, diagnostics and management of viral infections.
Here, we adapt this method for diagnostic use and probe its value in the monitoring of viral infections in immunocompromised individuals. We are studying the viral profiles of pediatric patients with primary immunodeficiencies (PID), as well as of immunosuppressed adults after transplantation (kidney and lung) and with acquired immunodeficiency (HIV). Patients participating in these studies are enrolled in approved clinical trials at the University Children’s Hospital and the University Hospital Zurich. The metagenomic sequence analysis is performed at the Institute of Medical Virology at the University of Zurich.
We anticipate that the obtained viral metagenomes will be instrumental in unraveling previously undetermined etiology of infections. The main value we expect from the proposed project is an advanced understanding of disease specific viruses, which may open avenues for improved treatment options, tailored diagnostics and reduced risk of nosocomial spread. While the virome analysis itself is cost intensive, we expect nevertheless a significant reduction of diagnostic expenses as repetitive testing for many putative pathogens can be omitted. Additionally, with personalized medicine aiming to utilize host gene information to shape medical care in the near future, an integrated analysis of the virome may allow defining which viral pathogen a given individual might be most vulnerable to.
- Establish and validate metagenomic virus analysis for routine diagnostic use
- Resolve etiology of infection using metagenomic virus profiling in settings where common virus diagnostics failed
- Dissect characteristics of virus profiles associated in disease-induced immunodeficiency
- Does information on the virome following lung and kidney transplantation improve our understanding of the potential risks in acquiring viral infections in the respective patients?
- To what extent does ongoing HIV influence the virome?
- Is the occurrence of certain viruses characteristic for specific immunodeficiencies and/or for a specific individual?
- Unravel virus profiles associated with genetic immunodeficiencies
- Are certain primary immunodeficiencies/genetic backgrounds associated with characteristic viral infections and/or a characteristic virus profile?
- Do defects in the same pathway lead to the same infections?
- Employ virus profiling to improve therapy
The subproject viral metagenomics comprises a network of immunologists, infectious disease specialist, transplantation specialists and virologists located at the University Hospital, the University Children’s Hospital and the University of Zurich. The organogram below indicates all involved parties.
University Hospital Zurich
Prof. Dr. med. Nicolas Müller (Project leader, Senior staff physician, Division of Infectious Diseases and Hospital Epidemiology; Chairman, Scientific Committee Swiss Transplant Cohort Study (STCS); Head, Transplant Center, University Hospital Zurich
PD Dr. med. Christian Benden (Senior staff physician, Director, Lung transplant program, University Hospital Zurich)
Dr. med. Macé Schuurmans (Staff physician, Lung transplant program)
Prof. Dr. med. Huldrych Günthard (Senior staff physician, Division of Infectious Diseases and Hospital Epidemiology)
PD Dr. med. Karin Metzner (Group leader)
Prof. Dr. med. Rainer Weber (Head, Division of Infectious Diseases and Hospital Epidemiology)
Dr. med. Benjamin Hampel
Institute of Medical Virology, University of Zurich
Prof. Dr. Alexandra Trkola (Project co-leader, Head of the Institute)
Dr. Michael Huber (Subproject leader diagnostics)
PD Dr. Jürg Böni (Head Diagnostics and Development)
PD Dr. Jovan Pavlovic (Group leader, innate control of viruses)
Dr. Osvaldo Zagordi (Bioinformatician)
Verena Kufner (PhD student)
Stefan Schmutz (Technician)
University Children’s Hospital Zurich
Prof. Dr. med. Janine Reichenbach (Co-Head Division Immunology)
Prof. Dr. med. Jana Pachlopnik Schmid, PhD (Co-Head Division Immunology)
PD Dr. med. Tayfun Güngör (Senior staff physician, Hemtopoetic stem cell transplantion unit)
Prof. em. Dr. med. Reinhard Seger (Director, Immunology, Hematology, Hemtopoetic stem cell transplantion unit)
Prof. Dr. med. David Nadal (Head, Infectious Diseases and Hospital Epidemiology)
Prof. Dr. med. Christoph Berger (Co-Head, Infectious Diseases and Hospital Epidemiology )