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https://hdl.handle.net/20.500.14094/0100477945
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2024-06-01
13:33 集計
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0100477945 (fulltext)
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0100477945
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open access
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タイトル
ATF1 Restricts Human Herpesvirus 6A Replication via Beta Interferon Induction
著者
Aktar, Salma ; Arii, Jun ; Thi Thu Huong Nguyen ; Huang, Jing Rin ; Nishimura, Mitsuhiro ; Mori, Yasuko
著者名
Aktar, Salma
著者ID
A2591
研究者ID
1000030704928
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=1f0aa402893ddbca520e17560c007669
著者名
Arii, Jun
有井, 潤
アリイ, ジュン
所属機関名
医学研究科
著者名
Thi Thu Huong Nguyen
著者名
Huang, Jing Rin
著者ID
A0486
研究者ID
1000040510285
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=8ba58502605c9ec6520e17560c007669
著者名
Nishimura, Mitsuhiro
西村, 光広
ニシムラ, ミツヒロ
所属機関名
医学研究科
著者ID
A0456
研究者ID
1000050343257
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=11c6b67469a01145520e17560c007669
著者名
Mori, Yasuko
森, 康子
モリ, ヤスコ
所属機関名
医学研究科
収録物名
Journal of Virology
巻(号)
96(19)
ページ
e01264-22
出版者
American Society for Microbiology
刊行日
2022-10-12
公開日
2023-04-01
抄録
The stimulus-induced cAMP response element (CRE)-binding protein (CREB) family of transcription factors bind to CREs to regulate diverse cellular responses, including proliferation, survival, and differentiation. Human herpesvirus 6A (HHV-6A), which belongs to the Betaherpesvirinae subfamily, is a lymphotropic herpesvirus frequently found in patients with neuroinflammatory diseases. Previous reports implicated the importance of CREs in the HHV-6A life cycle, although the effects of the binding of transcription factors to CREs in viral replication have not been fully elucidated. In this study, we analyzed the role of the CREB family of transcription factors during HHV-6A replication. We found that HHV-6A infection enhanced phosphorylation of the CREB family members CREB1 and activating transcription factor 1 (ATF1). Knockout (KO) of CREB1 or ATF1 enhanced viral gene expression and viral replication. The increase in viral yields in supernatants from ATF1-KO cells was greater than that in supernatants from CREB1-KO cells. Transcriptome sequencing (RNA-seq) analysis showed that sensors of the innate immune system were downregulated in ATF1-KO cells, and mRNAs of beta interferon (IFN-β) and IFN-regulated genes were reduced in these cells infected with HHV-6A. IFN-β treatment of ATF1-KO cells reduced progeny viral yields significantly, suggesting that the enhancement of viral replication was caused by a reduction of IFN-β. Taken together, our results suggest that ATF1 is activated during HHV-6A infection and restricts viral replication via IFN-β induction. IMPORTANCE Human herpesvirus 6A (HHV-6A) is a ubiquitous herpesvirus implicated in Alzheimer’s disease, although its role in its pathogenesis has not been confirmed. Here, we showed that the transcription factor ATF1 restricts HHV-6A replication, mediated by IFN-β induction. Our study provides new insights into the role of ATF1 in innate viral immunity and reveals the importance of IFN-β for regulation of HHV-6A replication, which possibly impairs HHV-6A pathogenesis.
キーワード
ATF1
HHV-6
gene expression
herpesviruses
interferons
transcription factors
カテゴリ
医学研究科
学術雑誌論文
権利
© 2022 American Society for Microbiology. All Rights Reserved.
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資源タイプ
journal article
言語
English (英語)
ISSN
0022-538X
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eISSN
1098-5514
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関連情報
DOI
https://doi.org/10.1128/jvi.01264-22
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