TY - JOUR
T1 - The encephalomyocarditis virus Leader promotes the release of virions inside extracellular vesicles via the induction of secretory autophagy
AU - van der Grein, Susanne G
AU - Defourny, Kyra A Y
AU - Rabouw, Huib H
AU - Goerdayal, Soenita S
AU - van Herwijnen, Martijn J C
AU - Wubbolts, Richard W
AU - Altelaar, Maarten
AU - van Kuppeveld, Frank J M
AU - Nolte-'t Hoen, Esther N M
N1 - Funding Information:
We are grateful to dr. Ger Arkesteijn for help with high-resolution flow cytometric analysis, as well as the Center for Cell Imaging Utrecht for allowing access to their facility for confocal imaging and training. We thank dr. Carla Ribeiro for providing antibodies against LC3 and Dr. Guillaume van Niel for helpful discussions. This work was supported by The Netherlands Organization for Scientific Research (NWO-ALW grant number ALWOP.351) ( https://www.nwo.nl/en ) as well as the European Research Council under the European Union’s Seventh Framework Program [FP/2007-2013] / ERC Grant Agreement number [337581] to E.N.M.N.tH. ( https://erc.europa.eu/funding/starting-grants ). This research was part of the Netherlands X-omics Initiative and partially funded by NWO (Project 184.034.019 to M.A.). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Naked viruses can escape host cells before the induction of lysis via release in extracellular vesicles (EVs). These nanosized EVs cloak the secreted virus particles in a host-derived membrane, which alters virus-host interactions that affect infection efficiency and antiviral immunity. Currently, little is known about the viral and host factors regulating this form of virus release. Here, we assessed the role of the encephalomyocarditis virus (EMCV) Leader protein, a 'viral security protein' that subverts the host antiviral response. EV release upon infection with wildtype virus or a Leader-deficient mutant was characterized at the single particle level using high-resolution flow cytometry. Inactivation of the Leader abolished EV induction during infection and strongly reduced EV-enclosed virus release. We demonstrate that the Leader promotes the release of virions within EVs by stimulating a secretory arm of autophagy. This newly discovered role of the EMCV Leader adds to the variety of mechanisms via which this protein affects virus-host interactions. Moreover, these data provide first evidence for a crucial role of a non-structural viral protein in the non-lytic release of picornaviruses via packaging in EVs.
AB - Naked viruses can escape host cells before the induction of lysis via release in extracellular vesicles (EVs). These nanosized EVs cloak the secreted virus particles in a host-derived membrane, which alters virus-host interactions that affect infection efficiency and antiviral immunity. Currently, little is known about the viral and host factors regulating this form of virus release. Here, we assessed the role of the encephalomyocarditis virus (EMCV) Leader protein, a 'viral security protein' that subverts the host antiviral response. EV release upon infection with wildtype virus or a Leader-deficient mutant was characterized at the single particle level using high-resolution flow cytometry. Inactivation of the Leader abolished EV induction during infection and strongly reduced EV-enclosed virus release. We demonstrate that the Leader promotes the release of virions within EVs by stimulating a secretory arm of autophagy. This newly discovered role of the EMCV Leader adds to the variety of mechanisms via which this protein affects virus-host interactions. Moreover, these data provide first evidence for a crucial role of a non-structural viral protein in the non-lytic release of picornaviruses via packaging in EVs.
KW - Antiviral Agents/metabolism
KW - Autophagy
KW - Encephalomyocarditis virus/metabolism
KW - Extracellular Vesicles/metabolism
KW - Viral Proteins/metabolism
KW - Virion/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85132917354&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-31181-y
DO - 10.1038/s41467-022-31181-y
M3 - Article
C2 - 35750662
SN - 2041-1723
VL - 13
SP - 1
EP - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3625
ER -