+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-7004 | |||||||||
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タイトル | Eilat virus/eastern equine encephalitis virus chimeric vaccine candidate | |||||||||
マップデータ | Eilat virus/eastern equine encephalitis virus chimeric vaccine candidate | |||||||||
試料 | Eilat virus/Eastern equine encephalitis virus chimera != Eilat virus Eilat virus/Eastern equine encephalitis virus chimera
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生物種 | Eilat virus (ウイルス) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 11.0 Å | |||||||||
データ登録者 | Sherman MB / Erasmus JH / Frolov I / Weaver SC / Nasar F | |||||||||
引用 | ジャーナル: J Virol / 年: 2018 タイトル: Novel Insect-Specific Eilat Virus-Based Chimeric Vaccine Candidates Provide Durable, Mono- and Multivalent, Single-Dose Protection against Lethal Alphavirus Challenge. 著者: Jesse H Erasmus / Robert L Seymour / Jason T Kaelber / Dal Y Kim / Grace Leal / Michael B Sherman / Ilya Frolov / Wah Chiu / Scott C Weaver / Farooq Nasar / 要旨: Most alphaviruses are mosquito borne and exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, and nonhuman primates. Recently, a host- ...Most alphaviruses are mosquito borne and exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, and nonhuman primates. Recently, a host-restricted, mosquito-borne alphavirus, Eilat virus (EILV), was described with an inability to infect vertebrate cells based on defective attachment and/or entry, as well as a lack of genomic RNA replication. We investigated the utilization of EILV recombinant technology as a vaccine platform against eastern (EEEV) and Venezuelan equine encephalitis viruses (VEEV), two important pathogens of humans and domesticated animals. EILV chimeras containing structural proteins of EEEV or VEEV were engineered and successfully rescued in cells. Cryo-electron microscopy reconstructions at 8 and 11 Å of EILV/VEEV and EILV/EEEV, respectively, showed virion and glycoprotein spike structures similar to those of VEEV-TC83 and other alphaviruses. The chimeras were unable to replicate in vertebrate cell lines or in brains of newborn mice when injected intracranially. Histopathologic examinations of the brain tissues showed no evidence of pathological lesions and were indistinguishable from those of mock-infected animals. A single-dose immunization of either monovalent or multivalent EILV chimera(s) generated neutralizing antibody responses and protected animals against lethal challenge 70 days later. Lastly, a single dose of monovalent EILV chimeras generated protective responses as early as day 1 postvaccination and partial or complete protection by day 6. These data demonstrate the safety, immunogenicity, and efficacy of novel insect-specific EILV-based chimeras as potential EEEV and VEEV vaccines. Mostly in the last decade, insect-specific viruses have been discovered in several arbovirus families. However, most of these viruses are not well studied and largely have been ignored. We explored the use of the mosquito-specific alphavirus EILV as an alphavirus vaccine platform in well-established disease models for eastern (EEE) and Venezuelan equine encephalitis (VEE). EILV-based chimeras replicated to high titers in a mosquito cell line yet retained their host range restriction in vertebrates both and In addition, the chimeras generated immune responses that were higher than those of other human and/or equine vaccines. These findings indicate the feasibility of producing a safe, efficacious, mono- or multivalent vaccine against the encephalitic alphaviruses VEEV and EEEV. Lastly, these data demonstrate how host-restricted, insect-specific viruses can be engineered to develop vaccines against related pathogenic arboviruses that cause severe disease in humans and domesticated animals. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_7004.map.gz | 69.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-7004-v30.xml emd-7004.xml | 11.1 KB 11.1 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_7004.png | 229.8 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-7004 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7004 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_7004_validation.pdf.gz | 77.8 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_7004_full_validation.pdf.gz | 76.9 KB | 表示 | |
XML形式データ | emd_7004_validation.xml.gz | 493 B | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7004 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7004 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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-マップ
ファイル | ダウンロード / ファイル: emd_7004.map.gz / 形式: CCP4 / 大きさ: 347.6 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Eilat virus/eastern equine encephalitis virus chimeric vaccine candidate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 2.35 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
-全体 : Eilat virus/Eastern equine encephalitis virus chimera
全体 | 名称: Eilat virus/Eastern equine encephalitis virus chimera |
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要素 |
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-超分子 #1: Eilat virus
超分子 | 名称: Eilat virus / タイプ: virus / ID: 1 / 親要素: 0 / NCBI-ID: 1231903 / 生物種: Eilat virus / ウイルスタイプ: VIRION / ウイルス・単離状態: OTHER / ウイルス・エンベロープ: Yes / ウイルス・中空状態: No |
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宿主 | 生物種: Aedes (カ) |
Host system | 生物種: Aedes albopictus (ヒトスジシマカ) / 組換細胞: C7/10 |
分子量 | 理論値: 42 MDa |
ウイルス殻 | Shell ID: 1 / T番号(三角分割数): 4 |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.4 構成要素:
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グリッド | モデル: Quantifoil R2/2 / 材質: COPPER | ||||||||||||
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | JEOL 2200FS |
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特殊光学系 | エネルギーフィルター - 名称: In-column Omega Filter |
撮影 | フィルム・検出器のモデル: GATAN ULTRASCAN 4000 (4k x 4k) 実像数: 126 / 平均電子線量: 20.0 e/Å2 |
電子線 | 加速電圧: 200 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
試料ステージ | 試料ホルダーモデル: GATAN 626 SINGLE TILT LIQUID NITROGEN CRYO TRANSFER HOLDER ホルダー冷却材: NITROGEN |
-画像解析
CTF補正 | ソフトウェア - 名称: IMAGIC (ver. 5) |
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最終 再構成 | 想定した対称性 - 点群: I (正20面体型対称) / アルゴリズム: FOURIER SPACE / 解像度のタイプ: BY AUTHOR / 解像度: 11.0 Å / 解像度の算出法: FSC 0.5 CUT-OFF / ソフトウェア - 名称: IMAGIC (ver. 5) / 使用した粒子像数: 2145 |
初期 角度割当 | タイプ: ANGULAR RECONSTITUTION / ソフトウェア - 名称: IMAGIC (ver. 5) |
最終 角度割当 | タイプ: PROJECTION MATCHING / ソフトウェア - 名称: IMAGIC (ver. 5) |