Reactivation of HSV-1 following explant of tree shrew brain
Li LH1,2; Li ZR2; Xia YJ3,4; Fraser NW5; Gao F[*]1; Zhou JM[*]2; Li X2; Wang RL2; Lang FC2
刊名JOURNAL OF NEUROVIROLOGY
2016
卷号22期号:3页码:293-306
关键词Treeshrew HSV-1 Latency Reactivation CNS Explantcocultivation
通讯作者gaofeng@jlu.edu.cn ; zhoujm@mail.kiz.ac.cn
合作状况其它
英文摘要Herpes Simplex Virus type I (HSV-1) latently infects peripheral nervous system (PNS) sensory neurons, and its reactivation leads to recurring cold sores. The reactivated HSV-1 can travel retrograde from the PNS into the central nervous system (CNS) and is known to be causative of Herpes Simplex viral encephalitis. HSV-1 infection in the PNS is well documented, but little is known on the fate of HSV-1 once it enters the CNS. In the murine model, HSV-1 genome persists in the CNS once infected through an ocular route. To gain more details of HSV-1 infection in the CNS, we characterized HSV-1 infection of the tree shrew (Tupaia belangeri chinensis) brain following ocular inoculation. Here, we report that HSV-1 enters the tree shrew brain following ocular inoculation and HSV-1 transcripts, ICP0, ICP4, and LAT can be detected at 5 days post-infection (p.i.), peaking at 10 days p.i. After 2 weeks, ICP4 and ICP0 transcripts are reduced to a basal level, but the LAT intron region continues to be expressed. Live virus could be recovered from the olfactory bulb and brain stem tissue. Viral proteins could be detected using anti-HSV-1 antibodies and anti-ICP4 antibody, during the acute stage but not beyond. In situ hybridization could detect LAT during acute infection in most brain regions and in olfactory bulb and brain stem tissue well beyond the acute stage. Using a homogenate from these tissues' post-acute infection, we did not recover live HSV-1 virus, supporting a latent infection, but using a modified explant cocultivation technique, we were able to recover reactivated virus from these tissues, suggesting that the HSV-1 virus latently infects the tree shrew CNS. Compared to mouse, the CNS acute infection of the tree shrew is delayed and the olfactory bulb contains most latent virus. During the acute stage, a portion of the infected tree shrews exhibit symptoms similar to human viral encephalitis. These findings, together with the fact that tree shrews are closely related to primates, provided a valuable alternative model to study HSV-1 infection and pathogenesis in the CNS.
收录类别SCI
语种英语
内容类型期刊论文
源URL[http://159.226.149.26:8080/handle/152453/10234]  
专题昆明动物研究所_基因调控与表达遗传
昆明动物研究所_动物模型与人类重大疾病机理重点实验室
昆明动物研究所_中国科学院昆明灵长类研究中心
作者单位1.Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, China
2.KeyLaboratoryofAnimalModelsandHumanDiseaseMechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
3.Kunming Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
4.Center for Drug Safety Evaluation, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
5.Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Li LH,Li ZR,Xia YJ,et al. Reactivation of HSV-1 following explant of tree shrew brain[J]. JOURNAL OF NEUROVIROLOGY,2016,22(3):293-306.
APA Li LH.,Li ZR.,Xia YJ.,Fraser NW.,Gao F[*].,...&Lang FC.(2016).Reactivation of HSV-1 following explant of tree shrew brain.JOURNAL OF NEUROVIROLOGY,22(3),293-306.
MLA Li LH,et al."Reactivation of HSV-1 following explant of tree shrew brain".JOURNAL OF NEUROVIROLOGY 22.3(2016):293-306.
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