The role of Extracellular Vesicles in picornavirus infections: Playing good cop, bad cop?

Summary

A central dogma in virology states that naked viruses spread by inducing cell lysis. Challenging new data indicate that naked picornaviruses also escape from intact cells enclosed in extracellular vesicles (EV). Release of EV by cells has come in the limelight as a widespread and conserved means of intercellular communication. Cellular activation/differentiation stimuli affect the molecular composition of EV, causing heterogeneity in EV phenotype and function. Current evidence that EV-enclosed virions can either benefit viral progression or strengthen host antiviral immunity has not been reconciled. Our data indicate that picornavirus infection not only causes escape of virions in EV, but also induces temporal release of other EV subpopulations. We hypothesize that pro- and anti-viral effects can be attributed to phenotypically different EV populations.
Aim: to delineate the role of EV in lytic virus infections by unravelling the structural and functional heterogeneity of virus-induced EV.
Key objectives: 1) To define EV subpopulations released from picornavirus-infected cells, based on molecular constituents of virus/host origin and temporal release. 2) To clarify if and how components of the innate immune system contribute to the formation and pro-/anti-viral functions of virus-induced EV subpopulations.
Approach: Using our single EV detection technology, which outperforms common analyses of bulk-isolated EV, different virus-induced EV will be quantified, characterized, and isolated. Moreover, strategies to interfere in EV formation and the host’s antiviral response will be used.
The outcome delineates how EV-enclosure impacts the picornavirus life cycle and clarifies how different virus-induced EV populations contribute to virus progression and antiviral immunity.

Details

Project number

ALWOP.351

Main applicant

Dr. E.N.M. Nolte-'t Hoen

Affiliated with

Universiteit Utrecht, Faculteit Diergeneeskunde, Departement Biochemie & Celbiologie

Duration

01/01/2018 to 01/01/2022

Budget

EUR276,474