Buckingham Erin M, Girsch James, Jackson Wallen, Cohen Jeffrey I, Grose Charles
Virology Laboratory, Children's Hospital, University of Iowa, Iowa City, IA, United States.
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
Front Microbiol. 2018 Dec 5;9:2935. doi: 10.3389/fmicb.2018.02935. eCollection 2018.
The goal of this project was to document the autophagy response in human neonatal skin organ culture (SOC) after infection with varicella-zoster virus (VZV). The VZV-infected SOC model has attributes of herpes zoster, in that an injection of virus into the skin is analogous to exit of virus from the sensory nerve termini into skin during herpes zoster. Cultures were maintained for 28 days and periodically examined for an autophagy response by quantitation of autophagosomes with Imaris software. Expression of the STAT3 protein was plentiful in the VZV-infected SOC. Abundant autophagy was observed in VZV-infected SOC between 14 and 28 days after infection, while autophagy in mock-infected SOC was minimal ( = 0.0003). The autophagic response after infection of SOC with a recombinant VZV genome containing the herpes simplex virus ICP34.5 neurovirulence gene was similar to wild-type VZV ( = 0.3). These results suggested that the VZV-infected SOC system resembled biopsy data from herpes zoster infection of skin. An enhanced autophagy response has now been reported after infection with two additional alpha herpesviruses besides VZV, namely, pseudorabies virus and duck enteritis herpes virus; both lack the ICP34.5 protein.
本项目的目标是记录人新生儿皮肤器官培养物(SOC)在感染水痘-带状疱疹病毒(VZV)后的自噬反应。VZV感染的SOC模型具有带状疱疹的特征,即向皮肤注射病毒类似于带状疱疹期间病毒从感觉神经末梢进入皮肤。培养物维持28天,并通过使用Imaris软件定量自噬体定期检测自噬反应。STAT3蛋白在VZV感染的SOC中表达丰富。在感染后14至28天期间,在VZV感染的SOC中观察到大量自噬,而在模拟感染的SOC中自噬极少(P = 0.0003)。用含有单纯疱疹病毒ICP34.5神经毒力基因的重组VZV基因组感染SOC后的自噬反应与野生型VZV相似(P = 0.3)。这些结果表明,VZV感染的SOC系统类似于皮肤带状疱疹感染的活检数据。现已报道,除VZV外,感染另外两种α疱疹病毒(即伪狂犬病病毒和鸭肠炎疱疹病毒)后自噬反应增强;这两种病毒都缺乏ICP34.5蛋白。