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 c...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-06-01
|
| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-022-00902-7 |
| _version_ | 1818545880262770688 |
|---|---|
| author | Yoshitaka Sato Masahiro Yaguchi Yusuke Okuno Hanako Ishimaru Ken Sagou Somi Ozaki Takeshi Suzuki Tomoki Inagaki Miki Umeda Takahiro Watanabe Masahiro Fujimuro Takayuki Murata Hiroshi Kimura |
| author_facet | Yoshitaka Sato Masahiro Yaguchi Yusuke Okuno Hanako Ishimaru Ken Sagou Somi Ozaki Takeshi Suzuki Tomoki Inagaki Miki Umeda Takahiro Watanabe Masahiro Fujimuro Takayuki Murata Hiroshi Kimura |
| author_sort | Yoshitaka Sato |
| collection | DOAJ |
| description | 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 Video abstract |
| first_indexed | 2024-12-12T07:45:46Z |
| format | Article |
| id | doaj.art-6dbc771c50774bf085446fa553b5b517 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-12-12T07:45:46Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-6dbc771c50774bf085446fa553b5b5172022-12-22T00:32:36ZengBMCCell Communication and Signaling1478-811X2022-06-0120111210.1186/s12964-022-00902-7Epstein–Barr virus tegument protein BGLF2 in exosomes released from virus-producing cells facilitates de novo infectionYoshitaka Sato0Masahiro Yaguchi1Yusuke Okuno2Hanako Ishimaru3Ken Sagou4Somi Ozaki5Takeshi Suzuki6Tomoki Inagaki7Miki Umeda8Takahiro Watanabe9Masahiro Fujimuro10Takayuki Murata11Hiroshi Kimura12Department of Virology, Nagoya University Graduate School of MedicineDepartment of Virology, Nagoya University Graduate School of MedicineDepartment of Virology, Graduate School of Medicine, Nagoya City UniversityDepartment of Cell Biology, Kyoto Pharmaceutical UniversityDepartment of Virology, Nagoya University Graduate School of MedicineDepartment of Virology, Nagoya University Graduate School of MedicineDepartment of Virology, Nagoya University Graduate School of MedicineDepartment of Virology, Nagoya University Graduate School of MedicineDepartment of Virology, Nagoya University Graduate School of MedicineDepartment of Virology, Nagoya University Graduate School of MedicineDepartment of Cell Biology, Kyoto Pharmaceutical UniversityDepartment of Virology, Nagoya University Graduate School of MedicineDepartment of Virology, Nagoya University Graduate School of MedicineAbstract 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 Video abstracthttps://doi.org/10.1186/s12964-022-00902-7Epstein–Barr virusExosomeBGLF2De novo infectionExtraviral particle |
| spellingShingle | Yoshitaka Sato Masahiro Yaguchi Yusuke Okuno Hanako Ishimaru Ken Sagou Somi Ozaki Takeshi Suzuki Tomoki Inagaki Miki Umeda Takahiro Watanabe Masahiro Fujimuro Takayuki Murata Hiroshi Kimura Epstein–Barr virus tegument protein BGLF2 in exosomes released from virus-producing cells facilitates de novo infection Cell Communication and Signaling Epstein–Barr virus Exosome BGLF2 De novo infection Extraviral particle |
| title | Epstein–Barr virus tegument protein BGLF2 in exosomes released from virus-producing cells facilitates de novo infection |
| title_full | Epstein–Barr virus tegument protein BGLF2 in exosomes released from virus-producing cells facilitates de novo infection |
| title_fullStr | Epstein–Barr virus tegument protein BGLF2 in exosomes released from virus-producing cells facilitates de novo infection |
| title_full_unstemmed | Epstein–Barr virus tegument protein BGLF2 in exosomes released from virus-producing cells facilitates de novo infection |
| title_short | Epstein–Barr virus tegument protein BGLF2 in exosomes released from virus-producing cells facilitates de novo infection |
| title_sort | epstein barr virus tegument protein bglf2 in exosomes released from virus producing cells facilitates de novo infection |
| topic | Epstein–Barr virus Exosome BGLF2 De novo infection Extraviral particle |
| url | https://doi.org/10.1186/s12964-022-00902-7 |
| work_keys_str_mv | AT yoshitakasato epsteinbarrvirustegumentproteinbglf2inexosomesreleasedfromvirusproducingcellsfacilitatesdenovoinfection AT masahiroyaguchi epsteinbarrvirustegumentproteinbglf2inexosomesreleasedfromvirusproducingcellsfacilitatesdenovoinfection AT yusukeokuno epsteinbarrvirustegumentproteinbglf2inexosomesreleasedfromvirusproducingcellsfacilitatesdenovoinfection AT hanakoishimaru epsteinbarrvirustegumentproteinbglf2inexosomesreleasedfromvirusproducingcellsfacilitatesdenovoinfection AT kensagou epsteinbarrvirustegumentproteinbglf2inexosomesreleasedfromvirusproducingcellsfacilitatesdenovoinfection AT somiozaki epsteinbarrvirustegumentproteinbglf2inexosomesreleasedfromvirusproducingcellsfacilitatesdenovoinfection AT takeshisuzuki epsteinbarrvirustegumentproteinbglf2inexosomesreleasedfromvirusproducingcellsfacilitatesdenovoinfection AT tomokiinagaki epsteinbarrvirustegumentproteinbglf2inexosomesreleasedfromvirusproducingcellsfacilitatesdenovoinfection AT mikiumeda epsteinbarrvirustegumentproteinbglf2inexosomesreleasedfromvirusproducingcellsfacilitatesdenovoinfection AT takahirowatanabe epsteinbarrvirustegumentproteinbglf2inexosomesreleasedfromvirusproducingcellsfacilitatesdenovoinfection AT masahirofujimuro epsteinbarrvirustegumentproteinbglf2inexosomesreleasedfromvirusproducingcellsfacilitatesdenovoinfection AT takayukimurata epsteinbarrvirustegumentproteinbglf2inexosomesreleasedfromvirusproducingcellsfacilitatesdenovoinfection AT hiroshikimura epsteinbarrvirustegumentproteinbglf2inexosomesreleasedfromvirusproducingcellsfacilitatesdenovoinfection |