The S segment of Punta Toro virus (Bunyaviridae, Phlebovirus) is a major determinant of lethality in the Syrian hamster and codes for a type I interferon antagonist
The S segment of Punta Toro virus (Bunyaviridae, Phlebovirus) is a major determinant of lethality in the Syrian hamster and codes for a type I interferon antagonist
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DOI：
10.1128/jvi.01074-06
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发表时间：
2007-01-01
影响因子：
5.4
通讯作者：
Peters, C. J.
中科院分区：
文献类型：
--
作者：
Perrone, Lucy A.;Narayanan, Krishna;Peters, C. J.
两株蓬塔托罗病毒（PTV），分离自发热的人在巴拿马，引起不同的发病机制，在叙利亚仓鼠，这可能是一个有用的模型，了解其他静脉病毒感染，如裂谷热病毒的毒力特征和不同的结果。本研究使用致死性Adames（A/A/A）和非致死性Balliet（B/B/B）毒株之间产生的遗传抑制物，研究仓鼠模型中致病性和致死性的病毒遗传决定因素。S区段被揭示为关键基因组区段，如下（L/M/S惯例）确定每种PTV基因型的对数50%致死剂量的致死率：A/A/A，<0.7; B/A/A，< 0.7; A/B/A，1.5; B/B/A，2.2; B/A/B，4.7; A/B/B，> 4.7; A/A/B，> 4.7; B/B/B，> 4.7。此外，Adames菌株在体内和体外抑制α/β干扰素（IFN-α/β）的诱导，并抑制IFN-β启动子的活化。PTV Adames NSs蛋白的表达，由S RNA片段编码，抑制病毒介导的IFN-β启动子驱动的报告基因的诱导，表明PTV NSs作为I型IFN拮抗剂发挥作用。两者合计，这些数据表明，在PTV感染早期抑制I型IFN应答导致早期和不受控制的病毒复制，并最终导致仓鼠死亡的发病机制。这项研究有助于我们理解白蛉病毒的发病机制，并确定潜在的免疫调节，以增加宿主的生存目标。
Two strains of Punta Toro virus (PTV), isolated from febrile humans in Panama, cause a differential pathogenesis in Syrian hamsters, which could be a useful model for understanding the virulence characteristics and differential outcomes in other phleboviral infections such as Rift Valley fever virus. Genetic reassortants produced between the lethal Adames (A/A/A) and nonlethal Balliet (B/B/B) strains were used in this study to investigate viral genetic determinants for pathogenesis and lethality in the hamster model. The S segment was revealed to be a critical genome segment, determining lethality with log,, 50% lethal doses for each PTV genotype as follows (L/M/S convention): A/A/A, < 0.7; B/A/A, < 0.7; A/B/A, 1.5; B/B/A, 2.2; B/A/B, 4.7; A/B/B, > 4.7; A/A/B, > 4.7; B/B/B, > 4.7. In addition, the Adames strain inhibits the induction of alpha/beta interferon (IFN-alpha/beta) in vivo and in vitro and inhibits the activation of the IFN-beta promoter. Expression of the PTV Adames NSs protein, encoded by the S RNA segment, inhibited the virus-mediated induction of an IFN-beta promoter-driven reporter gene, suggesting that PTV NSs functions as a type I IFN antagonist. Taken together, these data indicate a mechanism of pathogenesis in which the suppression of the type I IFN response early during PTV infection leads to early and uncontrolled viral replication and, ultimately, hamster death. This study contributes to our understanding of Phlebovirus pathogenesis and identifies potential targets for immune modulation to increase host survival.