Exosomes in the life cycle of viruses and the pathogenesis of viral infections

Abstract

Exosomes are extracellular vesicles of endosomal origin, with a bilayer membrane, 30160 nm in diameter. Exosomes are released from cells of different origins and are detected in various body fluids. They contain nucleic acids, proteins, lipids, metabolites and can transfer the contents to recipient cells. Exosome biogenesis involves cellular proteins of the Rab GTPase family and the ESCRT system, which regulate budding, vesicle transport, molecule sorting, membrane fusion, formation of multivesicular bodies and exosome secretion. Exosomes are released from cells infected with viruses and may contain viral DNA and RNA, as well as mRNA, microRNA, other types of RNA, proteins and virions. Exosomes are capable of transferring viral components into uninfected cells of various organs and tissues. This review analyzes the impact of exosomes on the life cycle of widespread viruses that cause serious human diseases: human immunodeficiency virus (HIV-1), hepatitis B virus, hepatitis C virus, SARS-CoV-2. Viruses are able to enter cells by endocytosis, use molecular and cellular pathways involving Rab and ESCRT proteins to release exosomes and spread viral infections. It has been shown that exosomes can have multidirectional effects on the pathogenesis of viral infections, suppressing or enhancing the course of diseases. Exosomes can potentially be used in noninvasive diagnostics as biomarkers of the stage of infection, and exosomes loaded with biomolecules and drugs - as therapeutic agents. Genetically modified exosomes are promising candidates for new antiviral vaccines.