Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA.
J Virol. 2013 Apr;87(7):3710-8. doi: 10.1128/JVI.02506-12. Epub 2013 Jan 16.
Toscana virus (TOSV), which is transmitted by Phlebotomus spp. sandflies, is a major etiologic agent of aseptic meningitis and encephalitis in the Mediterranean. Like other members of the genus Phlebovirus of the family Bunyaviridae, TOSV encodes a nonstructural protein (NSs) in its small RNA segment. Although the NSs of Rift Valley fever virus (RVFV) has been identified as an important virulence factor, which suppresses host general transcription, inhibits transcription from the beta interferon promoter, and promotes the proteasomal degradation of double-stranded RNA-dependent protein kinase (PKR), little is known about the functions of NSs proteins encoded by less-pathogenic members of this genus. In this study we report that TOSV is able to downregulate PKR with similar efficiency as RVFV, while infection with the other phleboviruses-i.e., Punta Toro virus, sandfly fever Sicilian virus, or Frijoles virus-has no effect on cellular PKR levels. In contrast to RVFV, however, cellular transcription remains unaffected during TOSV infection. TOSV NSs protein promotes the proteasome-dependent downregulation of PKR and is able to interact with kinase-inactive PKR in infected cells.
托斯卡纳病毒（TOSV）通过沙蝇属的沙蝇传播，是地中海地区无菌性脑膜炎和脑炎的主要病原体。与 Bunyaviridae 科的 Phlebovirus 属的其他成员一样，TOSV 在其小 RNA 片段中编码非结构蛋白（NSs）。虽然裂谷热病毒（RVFV）的 NSs 已被确定为一种重要的毒力因子，它可以抑制宿主的一般转录，抑制β干扰素启动子的转录，并促进双链 RNA 依赖性蛋白激酶（PKR）的蛋白酶体降解，但对于该属的致病性较低的成员编码的 NSs 蛋白的功能知之甚少。在这项研究中，我们报告说 TOSV 能够以与 RVFV 相似的效率下调 PKR，而感染其他沙蝇病毒 - 即蓬塔托罗病毒、西西里发热沙蝇病毒或弗里霍莱斯病毒 - 对细胞 PKR 水平没有影响。然而，与 RVFV 不同的是，细胞转录在 TOSV 感染期间不受影响。TOSV NSs 蛋白促进蛋白酶体依赖性 PKR 下调，并能够在感染细胞中与激酶失活的 PKR 相互作用。
