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© Research
Publication : Biophysical journal

Modeling the step of endosomal escape during cell infection by a nonenveloped virus

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Biophysical journal - 06 Mar 2012

Lagache T, Danos O, Holcman D

Link to Pubmed [PMID] – 22404920

Biophys. J. 2012 Mar;102(5):980-9

Widely disparate viruses enter the host cell through an endocytic pathway and travel the cytoplasm inside an endosome. For the viral genetic material to be delivered into the cytoplasm, these viruses have to escape the endosomal compartment, an event triggered by the conformational changes of viral endosomolytic proteins. We focus here on small nonenveloped viruses such as adeno-associated viruses, which contain few penetration proteins. The first time a penetration protein changes conformation defines the slowest timescale responsible for the escape. To evaluate this time, we construct what to our knowledge is a novel biophysical model based on a stochastic approach that accounts for the small number of proteins, the endosomal maturation, and the protease activation dynamics. We show that the escape time increases with the endosomal size, whereas decreasing with the number of viral particles inside the endosome. We predict that the optimal escape probability is achieved when the number of proteases in the endosome is in the range of 250-350, achieved for three viral particles.

https://www.ncbi.nlm.nih.gov/pubmed/22404920