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

Abstract:

: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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Lagache T,Danos O,Holcman D

doi

10.1016/j.bpj.2011.12.037

subject

Has Abstract

pub_date

2012-03-07 00:00:00

pages

980-9

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(11)05468-3

journal_volume

102

pub_type

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