Functional Importance of Hydrophobic Patches on the Ebola Virus VP35 IFN-Inhibitory Domain

Kasajima, Nodoka; Matsuno, Keita; Miyamoto, Hiroko; Kajihara, Masahiro; Igarashi, Manabu; Takada, Ayato

Functional Importance of Hydrophobic Patches on the Ebola Virus VP35 IFN-Inhibitory Domain

Kasajima, Nodoka; Matsuno, Keita; Miyamoto, Hiroko et al.

Viruses-Basel, 2021, 13(11), 2316

Permalink : https://hdl.handle.net/2115/83641

このアイテムのアクセス数:402件（2026-03-05 03:12 集計）

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アクセス権	metadata only access
URI	https://hdl.handle.net/2115/83641
タイトル	Functional Importance of Hydrophobic Patches on the Ebola Virus VP35 IFN-Inhibitory Domain
著者	Kasajima, Nodoka ; Matsuno, Keita ; Miyamoto, Hiroko ; Kajihara, Masahiro ; Igarashi, Manabu ; Takada, Ayato
著者名 Kasajima, Nodoka
e-Rad_Researcher 40753306 著者名 Matsuno, Keita
著者名 Miyamoto, Hiroko
e-Rad_Researcher 70711894 著者名 Kajihara, Masahiro
e-Rad_Researcher 10374240 著者名 Igarashi, Manabu
e-Rad_Researcher 10292062 著者名 Takada, Ayato
言語	英語
キーワード	Ebola virus
	VP35
	polymerase cofactor
	interferon antagonist
	IFN-inhibitory domain
	hydrophobic patch
発行日	2021-11
出版者	MDPI
収録物名	Viruses-Basel
巻(号)	13(11)
ページ	2316
抄録	Viral protein 35 (VP35) of Ebola virus (EBOV) is a multifunctional protein that mainly acts as a viral polymerase cofactor and an interferon antagonist. VP35 interacts with the viral nucleoprotein (NP) and double-stranded RNA for viral RNA transcription/replication and inhibition of type I interferon (IFN) production, respectively. The C-terminal portion of VP35, which is termed the IFN-inhibitory domain (IID), is important for both functions. To further identify critical regions in this domain, we analyzed the physical properties of the surface of VP35 IID, focusing on hydrophobic patches, which are expected to be functional sites that are involved in interactions with other molecules. Based on the known structural information of VP35 IID, three hydrophobic patches were identified on its surface and their biological importance was investigated using minigenome and IFN-beta promoter-reporter assays. Site-directed mutagenesis revealed that some of the amino acid substitutions that were predicted to disrupt the hydrophobicity of the patches significantly decreased the efficiency of viral genome replication/transcription due to reduced interaction with NP, suggesting that the hydrophobic patches might be critical for the formation of a replication complex through the interaction with NP. It was also found that the hydrophobic patches were involved in the IFN-inhibitory function of VP35. These results highlight the importance of hydrophobic patches on the surface of EBOV VP35 IID and also indicate that patch analysis is useful for the identification of amino acid residues that directly contribute to protein functions.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
PISSN	1999-4915
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.3390/v13112316