Infection with flaviviruses requires BCLXL for cell survival

Suzuki, Tatsuya; Okamoto, Toru; Katoh, Hiroshi; Sugiyama, Yukari; Kusakabe, Shinji; Tokunaga, Makoto; Hirano, Junki; Miyata, Yuka; Fukuhara, Takasuke; Ikawa, Masahito; Satoh, Takashi; Yoshio, Sachiyo; Suzuki, Ryosuke; Saijo, Masayuki; Huang, David C.S.; Kanto, Tatsuya; Akira, Shizuo; Matsuura, Yoshiharu

doi:https://doi.org/10.1371/journal.ppat.1007299

Infection with flaviviruses requires BCLXL for cell survival

Suzuki, Tatsuya; Okamoto, Toru; Katoh, Hiroshi et al.

PLoS Pathogens, 2018, 14(9), e1007299

アクセス数:595件（2025-04-18 02:35 集計）

固定URL: https://hdl.handle.net/11094/78571

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タイトル	Infection with flaviviruses requires BCLXL for cell survival
著者	NRID 1000010837272 1000010837272 researchmap permalink tatsuya-suzuki tatsuya-suzuki Scopus Author ID 57171130500 57171130500 著者名 Suzuki, Tatsuya
	NRID 1000080628595 1000080628595 researchmap permalink TOKAMOTO TOKAMOTO Scopus Author ID 10144905800 10144905800 著者名 Okamoto, Toru
	著者名 Katoh, Hiroshi
	著者名 Sugiyama, Yukari
	著者名 Kusakabe, Shinji
	著者名 Tokunaga, Makoto
	NRID 1000050899101 1000050899101 researchmap permalink 50899101 50899101 著者名 Hirano, Junki
	著者名 Miyata, Yuka
	NRID 1000070598739 1000070598739 著者名 Fukuhara, Takasuke
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 著者名 Ikawa, Masahito
	著者名 Satoh, Takashi
	NRID 1000010774060 1000010774060 著者名 Yoshio, Sachiyo
	NRID 1000050342902 1000050342902 著者名 Suzuki, Ryosuke
	NRID 1000050300926 1000050300926 著者名 Saijo, Masayuki
	著者名 Huang, David C.S.
	NRID 1000080372613 1000080372613 著者名 Kanto, Tatsuya
	NRID 1000050192919 1000050192919 researchmap permalink read0191262 read0191262 Scopus Author ID 35396685700 35396685700 著者名 Akira, Shizuo
	NRID 1000050157252 1000050157252 ORCID 0000-0001-9091-8285 0000-0001-9091-8285 researchmap permalink matsuura_123 matsuura_123 Scopus Author ID 7202988996 7202988996 著者名 Matsuura, Yoshiharu
内容	Infection with flaviviruses requires BCLXL for cell survival. Suzuki T, Okamoto T, Katoh H, Sugiyama Y, Kusakabe S, et al. PLOS Pathogens. 2018. 14(9): e1007299. doi:10.1371/journal.ppat.1007299
抄録	BCL2 family proteins including pro-survival proteins, BH3-only proteins and BAX/BAK proteins control mitochondria-mediated apoptosis to maintain cell homeostasis via the removal of damaged cells and pathogen-infected cells. In this study, we examined the roles of BCL2 proteins in the induction of apoptosis in cells upon infection with flaviviruses, such as Japanese encephalitis virus, Dengue virus and Zika virus. We showed that survival of the infected cells depends on BCLXL, a pro-survival BCL2 protein due to suppression of the expression of another pro-survival protein, MCL1. Treatment with BCLXL inhibitors, as well as deficient BCLXL gene expression, induced BAX/BAK-dependent apoptosis upon infection with flaviviruses. Flavivirus infection attenuates cellular protein synthesis, which confers reduction of short-half-life proteins like MCL1. Inhibition of BCLXL increased phagocytosis of virus-infected cells by macrophages, thereby suppressing viral dissemination and chemokine production. Furthermore, we examined the roles of BCLXL in the death of JEV-infected cells during in vivo infection. Haploinsufficiency of the BCLXL gene, as well as administration of BH3 mimetic compounds, increased survival rate after challenge of JEV infection and suppressed inflammation. These results suggest that BCLXL plays a crucial role in the survival of cells infected with flaviviruses, and that BCLXL may provide a novel antiviral target to suppress propagation of the family of Flaviviridae viruses.
出版者	Public Library of Science
収録物名	PLoS Pathogens
巻(号)	14(9)
ページ	e1007299
刊行年月	2018-09-27
言語	英語
ハンドルURL	https://hdl.handle.net/11094/78571
PISSN	15537366
eISSN	15537374
NCID	AA12072310
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1371/journal.ppat.1007299
関連情報 (isIdenticalTo)	PMID 30261081
アクセス権	open access
権利情報	© 2018 Suzuki et al. This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	PLoS Pathogens. 2018, 14(9), p. e1007299
DC.title	Infection with flaviviruses requires BCLXL for cell survival
DC.creator	Suzuki, Tatsuya
	Okamoto, Toru
	Katoh, Hiroshi
	Sugiyama, Yukari
	Kusakabe, Shinji
	Tokunaga, Makoto
	Hirano, Junki
	Miyata, Yuka
	Fukuhara, Takasuke
	Ikawa, Masahito
	Satoh, Takashi
	Yoshio, Sachiyo
	Suzuki, Ryosuke
	Saijo, Masayuki
	Huang, David C.S.
	Kanto, Tatsuya
	Akira, Shizuo
	Matsuura, Yoshiharu
DC.publisher	Public Library of Science
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2018-09-27
DC.identifier	https://doi.org/10.1371/journal.ppat.1007299
DC.description	Infection with flaviviruses requires BCLXL for cell survival. Suzuki T, Okamoto T, Katoh H, Sugiyama Y, Kusakabe S, et al. PLOS Pathogens. 2018. 14(9): e1007299. doi:10.1371/journal.ppat.1007299
DCTERMS.abstract	BCL2 family proteins including pro-survival proteins, BH3-only proteins and BAX/BAK proteins control mitochondria-mediated apoptosis to maintain cell homeostasis via the removal of damaged cells and pathogen-infected cells. In this study, we examined the roles of BCL2 proteins in the induction of apoptosis in cells upon infection with flaviviruses, such as Japanese encephalitis virus, Dengue virus and Zika virus. We showed that survival of the infected cells depends on BCLXL, a pro-survival BCL2 protein due to suppression of the expression of another pro-survival protein, MCL1. Treatment with BCLXL inhibitors, as well as deficient BCLXL gene expression, induced BAX/BAK-dependent apoptosis upon infection with flaviviruses. Flavivirus infection attenuates cellular protein synthesis, which confers reduction of short-half-life proteins like MCL1. Inhibition of BCLXL increased phagocytosis of virus-infected cells by macrophages, thereby suppressing viral dissemination and chemokine production. Furthermore, we examined the roles of BCLXL in the death of JEV-infected cells during in vivo infection. Haploinsufficiency of the BCLXL gene, as well as administration of BH3 mimetic compounds, increased survival rate after challenge of JEV infection and suppressed inflammation. These results suggest that BCLXL plays a crucial role in the survival of cells infected with flaviviruses, and that BCLXL may provide a novel antiviral target to suppress propagation of the family of Flaviviridae viruses.
DC.rights	© 2018 Suzuki et al. This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	78571
citation_title	Infection with flaviviruses requires BCLXL for cell survival
citation_author	Suzuki, Tatsuya
	Okamoto, Toru
	Katoh, Hiroshi
	Sugiyama, Yukari
	Kusakabe, Shinji
	Tokunaga, Makoto
	Hirano, Junki
	Miyata, Yuka
	Fukuhara, Takasuke
	Ikawa, Masahito
	Satoh, Takashi
	Yoshio, Sachiyo
	Suzuki, Ryosuke
	Saijo, Masayuki
	Huang, David C.S.
	Kanto, Tatsuya
	Akira, Shizuo
	Matsuura, Yoshiharu
citation_publisher	Public Library of Science
citation_language	英語
citation_date	2018-09-27
citation_journal_title	PLoS Pathogens
citation_volume	14
citation_issue	9
citation_firstpage	e1007299
citation_doi	https://doi.org/10.1371/journal.ppat.1007299
citation_pmid	30261081
citation_public_url	https://hdl.handle.net/11094/78571

Infection with flaviviruses requires BCLXL for cell survival

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