Researchers from the National Centre for Biotechnology (CNB-CSIC), have described the mechanism used by human reovirus, a pathogen that causes respiratory and digestive diseases in children and young people, to exit infected cells. This virus, that has also been related to the development of celiac disease, is capable of sequestering cellular lysosomes (organelles attached to the cell membrane) to transport infectious viral particles from inside the cell to the surface. The results of this research that could lead to the design of new antiviral drugs, have been published in the Journal of Cell Biology.
This project, led by Cristina Risco, principal investigator at the CNB-CSIC has applied advance microscopy and image analysis techniques to solve the reovirus egress mechanism in collaboration with Terence Dermody´s group at the University of Pittsburgh in the United States
Upon entry into the cell, the reovirus builds its replication platforms or viral factories using cell membranes. Inside these structures, new infectious viruses are formed which subsequently leave the cell to propagate infection.
Lysosome sequestration
"In healthy cells, the function of lysosomes is the degradation of cellular components. However, during reovirus infection, The virus takes over the cell lysosomes, changes their pH or degree of acidity, and uses them to its own benefit to transport the infectious viral particles from the replication platform to the cell surface”, "says Isabel Fernández de Castro, first author of the study.
The study, in collaboration with researchers from the University of Pittsburgh (United States), has been carried out using different cell types and different viral strains so it confirms the existence of a general, new mechanism of virus egress.
"We are working to identify the cellular and viral factors that participate in this new viral pathway, information that can be very important to design new broad-spectrum antiviral drugs, because viruses from different families often use organelles and common routes to infect the cells. Knowledge of the cell biology of the human reovirus can also help us enhance its use for cancer treatments, since it has the capacity to specifically destroy tumor cells, "adds Risco.
A modified lysosomal organelle mediates non-lytic egress of reovirus. I. Fernández de Castro, R. Tenorio, P. Ortega-González, J.J. Knowlton, P.F. Zamora, C.H. Lee, J.J. Fernández, T.S. Dermody, C. Risco. J. Cell Biol. 2020. DOI: 10.1083/jcb.201910131.