Abstract

Exosome Mimicry in Virus Infection: The Hepatitis A Virus Model

Gerardo Kaplan, Principal Investigator, FDA

Hepatitis A virus (HAV), a small positive-strand RNA non-enveloped virus, uses the exosome secretory machinery to exit the cell. Although HAV is mainly transmitted through the fecal-oral route by naked particles, infectious exosomes (exo-HAV) carrying HAV particles, free genomes, or both are found in blood. We showed that exo-HAV uses the HAVCR1/NPC1 pathway of exosome mimicry to infect cells, and that the cargo of free HAV genomes but not naked particles are mainly responsible for infectivity. We also showed that cargo loading into exo-HAV during infection is a dynamic process resulting in exosomes lacking naked HAV particles. Further research on the HAV exosome mimicry model will help unravel poorly understood exosome cargo-delivery pathways, develop therapeutics to prevent and treat HAV infection, and harness HAV biology to produce exosome-based drugs.