The infection of murine gammaherpesvirus-68 delays the early embryonic development of zebrafish

Jun Yan , Mengdie Chi , Jun Xiao , Meiling Liu , Hao Feng
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Abstract

Zebrafish is a model animal for aquaculture as well as bio-medicine. Murine gamma-herpesvirus 68 (MHV68) is widely regarded as a model for the study of human gamma herpesviruses such as Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, the infection of MHV68 on zebrafish was investigated through incubating fertilized zebrafish eggs with MHV68. The development of zebrafish delayed or stopped at early stage separately when the zebrafish eggs were incubated with MHV68 at different dose for 2 h. The lytic gene of MHV68, including ORF65, RTA and ORF57, were detected in the genome of larvae hatched from the infected eggs. The transcription of the latent gene LANA but not of these lytic genes was detected by RT-PCR. The mRNA level of growth factor TGF-β1, but not of FGF3, was obviously decreased in the larvae from the MHV68 treated eggs. The mRNA levels of cytokines, such as IFNφ3, ISG15 and TNFα, varied post MHV68 infection; however, the transcription of the cytosolic DNA sensors, including DDX41, DHX9 and cGAS, did not change significantly. Moreover, the data generated in zebrafish cell line demonstrated that MHV68 could infect ZF4 cells. All the data support the conclusion that MHV68 could infect zebrafish embryo in the egg envelope and go into latent infection, which will delay the development of the embryos through some unknown mechanism.

小鼠γ疱疹病毒68的感染可延缓斑马鱼早期胚胎发育
斑马鱼是水产养殖和生物医学的典范动物。鼠γ -疱疹病毒68 (MHV68)被广泛认为是研究人类γ -疱疹病毒如卡波西肉瘤相关疱疹病毒(KSHV)的模型。本研究通过用MHV68孵育斑马鱼受精卵来研究MHV68对斑马鱼的感染。不同剂量的MHV68在斑马鱼卵中孵育2 h后,斑马鱼的发育分别出现早期延迟或停止的现象。从感染的斑马鱼卵孵化出的幼虫基因组中检测到MHV68的裂解基因ORF65、RTA和ORF57。RT-PCR检测到潜伏基因LANA的转录,但未检测到这些裂解基因的转录。MHV68处理后的幼虫生长因子TGF-β1 mRNA水平明显降低,FGF3 mRNA水平不明显降低。MHV68感染后,IFNφ3、ISG15、TNFα等细胞因子mRNA水平发生变化;而胞质DNA传感器,包括DDX41、DHX9和cGAS的转录没有明显变化。此外,在斑马鱼细胞系中产生的数据表明,MHV68可以感染ZF4细胞。这些数据均支持MHV68可在斑马鱼卵包膜内感染胚胎并进入潜伏感染状态,从而通过某种未知的机制延缓胚胎的发育。
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2.40
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