The encephalomyocarditis virus Leader promotes the release of virions inside extracellular vesicles via the induction of secretory autophagy

• Published in: Nature communications 2022-06, Vol.13 (1), p.3625-3625, Article 3625
• Main Authors: van der Grein, Susanne G., Defourny, Kyra A. Y., Rabouw, Huib H., Goerdayal, Soenita S., van Herwijnen, Martijn J. C., Wubbolts, Richard W., Altelaar, Maarten, van Kuppeveld, Frank J. M., Nolte-‘t Hoen, Esther N. M.
• Format: Article
• Language: English
• Subjects: 13/106; 13/31; 14/19; 631/326/596/2557; 631/80/86/820; 82/1; 82/29; 82/58; Autophagy; Deficient mutant; Encephalomyocarditis virus - metabolism; Extracellular vesicles; Extracellular Vesicles - metabolism; Flow cytometry; Humanities and Social Sciences; Inactivation; Infections; Lysis; multidisciplinary; Packaging; Protein sorting signals; Proteins; Science; Science (multidisciplinary); Vesicles; Viral Proteins - metabolism; Virion - metabolism; Virions; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-31181-y

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. Picornaviruses can escape infected cells via packaging in extracellular vesicles (EVs). Here, van der Grein et al. show that the non-structural Leader protein of encephalomyocarditis virus (EMCV) promotes the release of EV-enclosed virus particles and provide evidence for a role of secretory autophagy in this process.