Epstein–Barr virus tegument protein BGLF2 in exosomes released from virus-producing cells facilitates de novo infection

Abstract

Background Viruses must adapt to the environment of their host cells to establish infection and persist. Diverse mammalian cells, including virus-infected cells, release extracellular vesicles such as exosomes containing proteins and miRNAs, and use these vesicles to mediate intercellular communication. However, the roles of exosomes in viral infection remain unclear. Results We screened viral proteins to identify those responsible for the exosome-mediated enhancement of Epstein–Barr virus (EBV) infection. We identified BGLF2 protein encapsulated in exosomes, which were released by EBV-infected cells. BGLF2 protein is a tegument protein that exists in the space between the envelope and nucleocapsid, and it is released into the cytoplasm shortly after infection. BGLF2 protein-containing exosomes enhanced viral gene expression and repressed innate immunity, thereby supporting the EBV infection. Conclusions The EBV tegument protein BGLF2 is encapsulated in exosomes and released by infected cells to facilitate the establishment of EBV infection. These findings suggest that tegument proteins support viral infection not only between the envelope and nucleocapsid, as well as in extraviral particles such as exosomes. Graphical abstract

Epstein-Barr virus lytic gene BNRF1 promotes B-cell lymphomagenesis via IFI27 upregulation

“…We could not eliminate the possibility that BNRF1 proteins were transferred from the occasional lytic-induced cells to the latently infected cells via extracellular vesicles (EVs) such as exosomes because BNRF1 proteins were incorporated into EVs [ 52 ].…”

“…Akata(-) cells, Akata/EBV-EGFP [ 53 ], and LCLs established by recombinant EBV infection were maintained in RPMI 1640 supplemented with 10%-15% FBS. AGS/EBV-EGFP cells (kindly gifted by Hironori Yoshiyama) [ 54 ] were grown in RPMI 1640 medium containing 10% FBS and 750 μg/mL G418 [ 55 ].…”

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