State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
BMC Genomics. 2018 Mar 20;19(1):211. doi: 10.1186/s12864-018-4596-y.
Ranaviruses (family Iridoviridae, nucleocytoplasmic large DNA viruses) have been reported as promiscuous pathogens of cold-blooded vertebrates. Rana grylio virus (RGV, a ranavirus), from diseased frog Rana grylio with a genome of 105.79 kb and Andrias davidianus ranavirus (ADRV), from diseased Chinese giant salamander (CGS) with a genome of 106.73 kb, contains 99% homologous genes.
To uncover the differences in virus replication and host responses under interspecies infection, we analyzed transcriptomes of CGS challenged with RGV and ADRV in different time points (1d, 7d) for the first time. A total of 128,533 unigenes were obtained from 820,858,128 clean reads. Transcriptome analysis revealed stronger gene expression of RGV than ADRV at 1 d post infection (dpi), which was supported by infection in vitro. RGV replicated faster and had higher titers than ADRV in cultured CGS cell line. RT-qPCR revealed the RGV genes including the immediate early gene (RGV-89R) had higher expression level than that of ADRV at 1 dpi. It further verified the acute infection of RGV in interspecies infection. The number of differentially expressed genes and enriched pathways from RGV were lower than that from ADRV, which reflected the variant host responses at transcriptional level. No obvious changes of key components in pathway "Antigen processing and presentation" were detected for RGV at 1 dpi. Contrarily, ADRV infection down-regulated the expression levels of MHC I and CD8. The divergent host immune responses revealed the differences between interspecies and natural infection, which may resulted in different fates of the two viruses. Altogether, these results revealed the differences in transcriptome responses among ranavirus interspecies infection of amphibian and new insights in DNA virus-host interactions in interspecies infection.
The DNA virus (RGV) not only expressed self-genes and replicated quickly after entry into host under interspecies infection, but also avoided the over-activation of host responses. The strategy could gain time for the survival of interspecies pathogen, and may provide opportunity for its adaptive evolution and interspecies transmission.
虹彩病毒(虹彩病毒科,核质大 DNA 病毒)已被报道为冷血脊椎动物的混杂病原体。来自患病的牛蛙(Rana grylio)的蛙病毒(RGV,一种虹彩病毒),基因组大小为 105.79 kb,以及来自患病的中国大鲵(CGS)的大鲵虹彩病毒(ADRV),基因组大小为 106.73 kb,含有 99%同源基因。
为了揭示种间感染下病毒复制和宿主反应的差异,我们首次分析了感染 RGV 和 ADRV 的中国大鲵在不同时间点(1d、7d)的转录组。从 820858128 个清洁读数中获得了 128533 个基因。转录组分析表明,在感染后 1 天(dpi),RGV 的基因表达比 ADRV 更强,这得到了体外感染的支持。RGV 在培养的中国大鲵细胞系中复制更快,滴度更高。RT-qPCR 显示,在 1 dpi 时,RGV 基因(包括即刻早期基因(RGV-89R))的表达水平高于 ADRV。这进一步验证了 RGV 在种间感染中的急性感染。RGV 的差异表达基因数量和富集途径低于 ADRV,这反映了转录水平上宿主反应的变异。在 1 dpi 时,未检测到 RGV 对途径“抗原加工和呈递”中的关键成分的明显变化。相反,ADRV 感染下调了 MHC I 和 CD8 的表达水平。不同的宿主免疫反应揭示了种间感染和自然感染之间的差异,这可能导致两种病毒的不同命运。总之,这些结果揭示了两栖动物虹彩病毒种间感染的转录组反应差异,并为种间感染中 DNA 病毒-宿主相互作用提供了新的见解。
在种间感染中,DNA 病毒(RGV)不仅在进入宿主后表达自身基因并快速复制,而且还避免了宿主反应的过度激活。该策略为种间病原体的生存争取了时间,并为其适应性进化和种间传播提供了机会。