International consortium to study link between RSV infection and chronic respiratory tract diseases

UMC Utrecht will lead an international consortium that will try to answer a key question that's in the mind of many pediatricians, infectiologists, pulmonologists and other health professionals: "Why are children that had an RSV infection in early childhood at increased risk of developing asthma later in life?" The project - which will run for five years - is funded by a HORIZON HLTH 2023 grant from the European Commission of € 7 million.

Chronic respiratory tract diseases such as asthma and COPD are non-communicable diseases for which infections by several respiratory viruses and genetics constitute major risk factors. The molecular and physiological mechanisms of how these viral infections cause and contribute to non-communicable disease development are unknown. The Respiratory Syncytial Virus (RSV) is a virus that infects nearly all infants before the age of 2 years and is linked to asthma development. However, it is not clear what changes in the immature lungs of susceptible infants that causes later asthma development. It's also not yet clear how to revert possible damage done by RSV infection to immature lungs.

Interdisciplinary approach

In the CLARITY (Causative Link between respirAtory syncytial viRus and chronic lung diseases: Identifying Targets for therapY) research consortium, the investigators will use an integrative approach to identify genetic risk factors and mechanisms underlying virus-induced asthma. Specifically, using two national cohorts (Estonian and Spanish), they will try to identify human genetic risk factors and RSV strains that contribute to severe bronchiolitis. They will also analyze how RSV perturbs intracellular networks to change cellular properties that trigger asthma development. In addition, researchers will use artificial intelligence-based techniques to integrate generated data with the current biological knowledge, to generate RSV-induced perturbation signatures and to identify druglike compounds that are able to revert the effects of the RSV-induced perturbations. Finally they will validate both mechanisms and candidate compounds in patient derived airway organoid models and, if promising, in a controlled human infection model trial.

Virus-triggered asthma

Immunologist Marianne Boes PhD (Center for Translational Immunology and Department of Pediatrics, UMC Utrecht) is CLARITY project coordinator and principal investigator. She explains: "CLARITY is expected to impact the understanding, prevention and possibly treatment of virus-triggered asthma. The results will enable the development of a genetic risk score for long-term asthma development that enables personalized prevention campaigns, which will be developed jointly with patient groups. The molecular mechanisms discovered, and the drug-like compounds that revert the perturbation signatures, will enable development of mechanism-targeted drugs. Fundamentally, the mechanisms identified in this specific model for a strong viral contribution to non-communicable disease will likely represent general mechanisms of how viral infections cause onset and development of other non-communicable diseases."

Impact

The expected outcomes of the project are of considerable socio-economic value, since they ultimately aim at reducing disease burden and promoting well-being and empowering patients, their caregivers and the public. The impact of the outcomes will be delivered at multiple levels and may contribute to advancing the management of respiratory diseases, providing to a certain extent real clinical utility, and improving public awareness of RSV and its link with chronic respiratory tract diseases such as asthma and COPD.

CLARITY consortium

In the CLARITY consortium – which will be coordinated by UMC Utrecht – nine partners from four EU countries will collaborate: one university, three clinical centers, one public health organization, three research institutions and one patient organization. The project – which will run for 5 years - is funded by a HORIZON HEALTH 2023 grant of € 7 million from the European Commission, of which close to € 2 million has been allocated to UMC Utrecht.