Development of a nonhuman primate model for dengue virus infection

开发登革热病毒感染的非人灵长类动物模型

• 批准号: 21780274
• 负责人: KOBAYASHI Takeshi
• 金额: $ 2.41万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21780274/
• 关键词: デングウイルス; サルモデル

To develop a nonhuman primate model for dengue virus (DV) infection, rhesus monkeys were inoculated with DV types 1 and 2. The DV types 1 and 2 induced viremia with duration from 2 to 3 days and a mean peak titer of 4×10^3 RNA copies/ml but infected monkeys showed no sign of dengue diseases even after inoculation of high virus doses. DV type 2 effectively replicates in MDM cells derived from bonnet monkeys compared to those derived from rhesus monkeys. These results suggest that bonnet monkey may be a useful model to study dengue disease.To improve a reverse genetics for tick-borne encephalitis virus (TBEV) which belongs to the same member of the Flavivirus genus as DV, we have constructed a plasmid-based infectious clone encoding full-length TBEV cDNA under control of the minimum cytomegalovirus promoter. Transfection of cells with the plasmid resulted in the production of infectious TBEV at high levels. Furthermore, we have developed homologous recombination-based reverse genetics for TBEV and DV. The reverse genetics approaches described here can be exploited for studies of DV replication and pathogenesis as powerful tools.

为了建立登革热病毒（DV）感染的非人灵长类动物模型，恒河猴接种了1型和2型DV。1型和2型病毒血症持续时间为2 ~ 3天，平均峰值滴度为4×10^3 RNA拷贝/ml，但感染的猴子即使在接种高剂量病毒后也没有出现登革热疾病的迹象。与来自恒河猴的MDM细胞相比，DV 2型在帽猴的MDM细胞中有效地复制。这些结果提示帽猴可能是研究登革热疾病的有用模型。为了提高与DV同属黄病毒属的蜱传脑炎病毒（TBEV）的反向遗传能力，在最小巨细胞病毒启动子的控制下，构建了一个编码TBEV全长cDNA的质粒感染克隆。用质粒转染细胞可产生高水平的感染性TBEV。此外，我们还开发了基于同源重组的TBEV和DV反向基因。这里描述的反向遗传学方法可以作为强大的工具用于DV复制和发病机制的研究。

项目成果

Identification of Reovirus Cell-tropism Determinants in Replication Protein mu2

复制蛋白 mu2 中呼肠孤病毒向细胞性决定因素的鉴定

• 发表时间: 2009
• 作者: Laura S.Ooms;Takeshi Kobavashi;Terence S.Dermody;James D.Chappell.
• 通讯作者: James D.Chappell.

The Reovirus m2 Protein Inhibits Interferon Signaling Through a Novel Mechanism Involving Nuclear Accumulation of Interferon Regulatory Factor-9

呼肠孤病毒 m2 蛋白通过涉及干扰素调节因子 9 核积聚的新机制抑制干扰素信号传导

• 发表时间: 2009
• 期刊: Journal of Virology 83
• 作者: Zurney;J.;T.Tobavashi;G.H.Holm;T.S.Dermody;B.Sherry.;笛吹達史;小林剛;笛吹達史;Jennifer Zurney
• 通讯作者: Jennifer Zurney

Strategies to Develop Recombinant Rotavirus

开发重组轮状病毒的策略

• 发表时间: 2009
• 作者: Shane D.Trask;Zenobia F.Taraporewala;Takeshi Kobavashi;Andrew J.Rolle;Terence S.Dermody;John T.Patton.
• 通讯作者: John T.Patton.

Identification of Functional Domains in Reovirus Replication Proteins μNS and μ2

• DOI: 10.1128/jvi.01495-08
• 发表时间: 2009-04-01
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Kobayashi, Takeshi;Ooms, Laura S.;Dermody, Terence S.
• 通讯作者: Dermody, Terence S.

新規組換え技術によるCCR5指向性clade C HIV-1株のenv領域を持ったSHIVの作製

使用新型重组技术生产具有 CCR5-tropic clade C HIV-1 毒株的 env 区域的 SHIV

• 发表时间: 2010
• 作者: 藤田泰久;大附寛幸;小林剛;三浦智行;五十嵐樹彦
• 通讯作者: 五十嵐樹彦