TY - JOUR
T1 - Epstein–Barr virus tegument protein BGLF2 in exosomes released from virus-producing cells facilitates de novo infection
AU - Sato, Yoshitaka
AU - Yaguchi, Masahiro
AU - Okuno, Yusuke
AU - Ishimaru, Hanako
AU - Sagou, Ken
AU - Ozaki, Somi
AU - Suzuki, Takeshi
AU - Inagaki, Tomoki
AU - Umeda, Miki
AU - Watanabe, Takahiro
AU - Fujimuro, Masahiro
AU - Murata, Takayuki
AU - Kimura, Hiroshi
N1 - Funding Information:
The authors thank Hironori Yoshiyama for providing invaluable materials; Yohei Yamauchi for comments on the manuscript; Daisuke Yuasa, Shingo Ochiai, Shuko Kumagai, Junko Kishikawa, and Tomoko Kunogi for technical supports; Minoru Tanaka and the Division for Medical Research Engineering, Nagoya University Graduate School of Medicine for FACS analysis.
Funding Information:
This work was supported in part by grants from the Japan Society for the Promotion of Science (JSPS) KAKENHI ( https://www.jsps.go.jp ) (Grant Numbers JP16H06231, JP19H04829, JP21K15448 to Y.S., and JP20H03493 to H.K.); the JST ( https://www.jst.go.jp ) PRESTO (Grant Number JPMJPR19H5) to Y.S.; the Japan Agency for Medical Research and Development (AMED, https://www.amed.go.jp ) (JP19fm0208016 and JP20wm0325012 to T.M., JP19ck0106517 to Y.O., and JP19jk0210023 and JP21wm0325042 to Y.S.); the Takeda Science Foundation ( https://www.takeda-sci.or.jp ) to Y.S. and T.M.; the Hori Sciences and Arts Foundation ( https://www.hori-foundation.or.jp ) to Y.S. and H.K.; the MSD Life Science Foundation ( https://www.msd-life-science-foundation.or.jp ) to Y.S.; the Uehara Memorial Foundation ( https://www.ueharazaidan.or.jp/ ) to H.K.; the Chemo-Sero-Therapeutic Research Institute ( https://www.kaketsuken.org ) to H.K.; and the Aichi Health Promotion Foundation ( https://www.ahpf.or.jp ) to Y.S. and Y.O.. H.I. was supported by the JSPS Research fellowship (19J23589). T.S. was supported by the Takeda Science Foundation scholarship.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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: [Figure not available: see fulltext.] [MediaObject not available: see fulltext.].
AB - 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: [Figure not available: see fulltext.] [MediaObject not available: see fulltext.].
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U2 - 10.1186/s12964-022-00902-7
DO - 10.1186/s12964-022-00902-7
M3 - Article
C2 - 35729616
AN - SCOPUS:85132250410
VL - 20
JO - Cell Communication and Signaling
JF - Cell Communication and Signaling
SN - 1478-811X
IS - 1
M1 - 95
ER -