Journal Article

Dissemination of the Flavivirus Subgenomic Replicon Genome and Viral Proteins by Extracellular Vesicles

Narita, Kentaro, Ishikawa, Tomohiro, Masuda, Michiaki, Matsuyama, Kinichi

2024

Overview

Extracellular vesicles (EVs) such as exosomes have been shown to play physiological roles in cell-to-cell communication by delivering various proteins and nucleic acids. In addition, several studies revealed that the EVs derived from the cells that are infected with certain viruses could transfer the full-length viral genomes, resulting in EVs-mediated virus propagation. However, the possibility cannot be excluded that the prepared EVs were contaminated with infectious viral particles. In this study, the cells that harbor subgenomic replicon derived from the Japanese encephalitis virus and dengue virus without producing any replication-competent viruses were employed as the EV donor. It was demonstrated that the EVs in the culture supernatants of those cells were able to transfer the replicon genome to other cells of various types. It was also shown that the EVs were incorporated by the recipient cells primarily through macropinocytosis after interaction with CD33 and Tim-1/Tim-4 on HeLa and K562 cells, respectively. Since the methods used in this study are free from contamination with infectious viral particles, it is unequivocally indicated that the flavivirus genome can be transferred by EVs from cell to cell, suggesting that this pathway, in addition to the classical receptor-mediated infection, may play some roles in the viral propagation and pathogenesis.

• Publisher: MDPI AG,MDPI
• Subject: Analysis / Animals / cell communication / Cell culture / Cell interactions / Cell Line / Cells / Contamination / Dengue fever / Dengue virus / Dengue Virus - genetics / Dengue Virus - physiology / Dengue viruses / Encephalitis / Encephalitis Virus, Japanese - genetics / Encephalitis Virus, Japanese - physiology / exosome / Exosomes / Experiments / extracellular vesicle / Extracellular vesicles / Extracellular Vesicles - genetics / Extracellular Vesicles - metabolism / Extracellular Vesicles - virology / Flavivirus - genetics / Flavivirus - physiology / Genes / Genome, Viral / Genomes / Genomics / Health aspects / HeLa Cells / Hepatitis C / HIV / Human immunodeficiency virus / Humans / Infections / Japanese encephalitis virus / K562 Cells / Laboratories / Leukemia / Methods / Nucleic acids / Pathogenesis / Pharmaceutical industry / Propagation / Proteins / replicon / Replicon - genetics / RNA polymerase / Scientific equipment and supplies industry / Subgenomic RNA / viral genome / Viral proteins / Viral Proteins - genetics / Viral Proteins - metabolism / Virus Replication / Viruses