Deng Fuyou, Nuss Donald L
Center for Biosystems Reseach, University of Maryland Biotechnology Institute, Shady Grove Campus, 9600 Gudelsky Drive, Rockville, MD 20850, USA.
J Virol. 2008 Jul;82(13):6369-78. doi: 10.1128/JVI.02638-07. Epub 2008 Apr 30.
The prototypic hypovirus CHV1-EP713, responsible for virulence attenuation (hypovirulence) of the chestnut blight fungus Cryphonectria parasitica, encodes two papain-like proteases, p29 and p48. Protein p29 has been shown to be dispensable for hypovirus RNA replication and to act as a suppressor of RNA silencing. Here we describe a role for p48 in hypovirus RNA propagation. CHV1-EP713 infectious cDNA clones in which the p48 coding region was deleted, Delta p48, were unable to establish infection in C. parasitica when introduced as a DNA form by transformation or as a coding strand transcript by electroporation. However, the Delta p48 mutant virus RNA was rescued when p48 was provided in trans. Surprisingly, the Delta p48 mutant viruses retained replication competence in the apparent absence of p48 following transmission to wild-type C. parasitica and successive subculturing. The replicating Delta p48 mutant virus was reduced in RNA accumulation by 60% both in the absence and presence of p48 provided in trans and was transmitted through asexual spores (conidia) at a rate 3 to 8% of that for full-length CHV1-EP713. Complementary analysis of strains expressing p48 or containing the replicating Delta p48 mutant virus showed that like p29, p48 contributes to virus-mediated suppression of host pigmentation and conidiation, although to a lesser extent, and is dispensable for hypovirus-mediated hypovirulence. The combined results suggest that papain-like protease p48 plays an essential role in the initiation but not the maintenance of virus RNA propagation and also contributes to the regulation of viral RNA accumulation and vertical transmission.
原型低毒病毒CHV1-EP713可导致栗疫病菌Cryphonectria parasitica的毒力减弱(低毒性),它编码两种木瓜蛋白酶样蛋白酶,即p29和p48。已证明蛋白质p29对于低毒病毒RNA复制并非必需,且可作为RNA沉默的抑制剂。在此,我们描述了p48在低毒病毒RNA传播中的作用。缺失p48编码区的CHV1-EP713感染性cDNA克隆(Δp48),通过转化以DNA形式导入或通过电穿孔以编码链转录本形式导入时,均无法在寄生隐孢壳菌中建立感染。然而,当通过反式提供p48时,Δp48突变病毒RNA得以拯救。令人惊讶的是,在传播至野生型寄生隐孢壳菌并连续传代后,Δp48突变病毒在明显缺乏p48的情况下仍保留复制能力。在不存在和存在反式提供的p48的情况下,复制的Δp48突变病毒的RNA积累均减少了60%,并且通过无性孢子(分生孢子)传播的速率仅为全长CHV1-EP713的3%至8%。对表达p48或含有复制型Δp48突变病毒的菌株进行的互补分析表明,与p29一样,p48有助于病毒介导的对宿主色素沉着和分生孢子形成的抑制,尽管程度较小,并且对于低毒病毒介导的低毒性并非必需。综合结果表明,木瓜蛋白酶样蛋白酶p48在病毒RNA传播的起始而非维持过程中起关键作用,并且也有助于调节病毒RNA的积累和垂直传播。