Release and functions of picornavirus-induced extracellular vesicles: Transportable information carriers during virus infection

Abstract

Extracellular vesicles (EVs) are lipid bilayer-enclosed particles released by various cell types, carrying proteins, lipids and nucleic acids. Acting as paracrine or endocrine messengers, EVs play crucial roles in both physiological and pathological processes, including viral infections, either benefiting the host or contributing to disease pathology. However, the mechanisms by which viruses modify the release and composition of EVs, as well as the roles EVs play during infection, remain poorly understood. This thesis investigates the role of EVs in infections with picornaviruses, a group of non-enveloped RNA viruses that infect vertebrates and cause a spectrum of human and animal diseases with large economic repercussions. Recent studies show that EVs can shield virus particles from recognition by neutralizing antibodies which are important for immune defense against these viruses. We explored how these EV-enclosed viruses are formed, how efficient they transmit infection, and whether immune cells would be able to recognize and respond to these virus-induced EVs. By analyzing two picornaviruses, EMCV and CVB3, we discovered that these viruses produce specific proteins, so-called “security proteins” that affect cellular signaling pathways, resulting in altered EV production. Additionally, we compared the infectivity of virus-containing EVs produced by different cell types and demonstrated that both donor and recipient cell types can affect infection efficiency. Furthermore, EVs induced by EMCV and CVB3 exhibit varying capabilities for infection. Beyond their pro-viral effects, we demonstrate that virus-induced EVs can be recognized by immune cells, especially monocytes, which respond by antiviral cytokine production. These findings provide new insights into the mechanisms of virus-induced EV release and the multifaceted roles of EVs during viral infection.