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Cytomegaloviruses reprogram lung phagocytes so that they produce viruses themselves and spread them in the lungs / Findings could enable new therapies / Study in the journal Cell

Around half of the population carries cytomegaloviruses. Scientists at the Medical Center - University of Freiburg have now been able to show that the viruses attack the most important immune cells in the lungs. The immune phagocytes, known as macrophages, are manipulated in such a way that they lose their defense function and spread the viruses in the lungs. This in turn makes it easier for other pathogens to attack and can lead to pneumonia and potentially further severe courses of infection if the immune system is weakened. The signaling pathways that have now been decoded provide important targets for new targeted therapies for particularly susceptible people, such as pregnant women and people after organ transplants. The study was published on June 10, 2021 in the renowned journal Cell.

"The manipulation of cytomegaloviruses is so massive that the phagocytes of the lungs almost completely lose their defense function. Even with molecular methods, the cells can hardly be identified," says Prof. Dr. Philipp Henneke, Head of the Department of Pediatric Infectiology and Rheumatology at the Center for Pediatrics at the Medical Center - University of Freiburg. He conducted the study together with Sebastian Baasch in collaboration with Dr. Zsolt Ruzsics from the Institute for Virology at the Medical Center - University of Freiburg.

The researchers have now been able to prove in mice that the virus interferes with the so-called Wnt signaling pathway. "This transforms the reprogrammed cells into virus factories and contributes - via a profound change in their mobility - to the distribution of the virus in the lungs," says Baasch.

Hope for a better therapy for particularly susceptible people

Infection with cytomegalovirus (CMV) often occurs in infancy. The viruses then remain in the body permanently - usually without causing any symptoms. However, if the immune system is weakened, for example due to cancer, during pregnancy or in newborns, damage to the lungs, eyes and internal organs such as the intestines or liver can occur. The therapeutic options for complicated CMV infections are still very unsatisfactory. This is where the new findings of the Freiburg scientists come in. "The elucidation of molecular switches through which CMV manipulates our immune system is a step towards the development of new therapeutic approaches," says Henneke.

Original title of the publication: Cytomegalovirus subverts macrophage identity

DOI: https://doi.org/10.1016/j.cell.2021.05.009

Link to the study: https://authors.elsevier.com/c/1dDNgL7PXe~cx

Contact:
Prof. Dr. Philipp Henneke
Head of the Section for Pediatric Infectiology and Rheumatology
Center for Pediatrics
Medical Center - University of Freiburg
Phone: 0761 270-77640
philipp.henneke@uniklinik-freiburg.de