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Functional Importance of Hydrophobic Patches on the Ebola Virus VP35 IFN-Inhibitory Domain
| Title: | Functional Importance of Hydrophobic Patches on the Ebola Virus VP35 IFN-Inhibitory Domain |
| Authors: | Kasajima, Nodoka Browse this author | | Matsuno, Keita Browse this author →KAKEN DB | | Miyamoto, Hiroko Browse this author | | Kajihara, Masahiro Browse this author →KAKEN DB | | Igarashi, Manabu Browse this author →KAKEN DB | | Takada, Ayato Browse this author →KAKEN DB |
| Keywords: | Ebola virus | | VP35 | | polymerase cofactor | | interferon antagonist | | IFN-inhibitory domain | | hydrophobic patch |
| Issue Date: | Nov-2021 |
| Publisher: | MDPI |
| Journal Title: | Viruses-Basel |
| Volume: | 13 |
| Issue: | 11 |
| Start Page: | 2316 |
| Publisher DOI: | 10.3390/v13112316 |
| Abstract: | 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/83641 |
| Appears in Collections: | 人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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