A STING inhibitor suppresses EBV‐induced B cell transformation and lymphomagenesis

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

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“…The primer sequences used in this study are listed in Table 1 . Other primer information was described previously [ 52 ].…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2022

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“…DMSO or MMF (120 mg/kg) was administered orally. Viral DNA in the mouse blood was quantified, and a histological analysis was performed as previously described ( 91 ).…”

Section: Methodsmentioning

confidence: 99%

Growth Transformation of B Cells by Epstein-Barr Virus Requires IMPDH2 Induction and Nucleolar Hypertrophy

et al. 2023

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EBV infections cause nucleolar enlargement via the induction of IMPDH2, which are essential for B cell growth transformation by EBV. Although the significance of IMPDH2 induction and nuclear hypertrophy in the tumorigenesis of glioblastoma has been reported, EBV infection brings about the change quickly by using its transcriptional cofactor, EBNA2, and MYC. Moreover, we present here, for the novel, basic evidence that an IMPDH2 inhibitor, namely, MPA or MMF, can be used for EBV-positive posttransplant lymphoproliferative disorder (PTLD).

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“…The number of virus particles released into culture medium from lytically induced cells was quantified by enumerating viral genome copies as reported previously ( 59 ). Briefly, 200 μL of culture supernatant was pretreated with Turbo DNase I (Invitrogen) to remove free DNA.…”

Section: Methodsmentioning

confidence: 99%

Epstein-Barr Virus BBLF1 Mediates Secretory Vesicle Transport to Facilitate Mature Virion Release

Uddin

Watanabe

Arata

et al. 2023

J Virol

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A STING inhibitor suppresses EBV‐induced B cell transformation and lymphomagenesis

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 7 publications

References 61 publications

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

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

Growth Transformation of B Cells by Epstein-Barr Virus Requires IMPDH2 Induction and Nucleolar Hypertrophy

Epstein-Barr Virus BBLF1 Mediates Secretory Vesicle Transport to Facilitate Mature Virion Release

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