Reactivation of HSV-1 following explant of tree shrew brain

	Reactivation of HSV-1 following explant of tree shrew brain
	Li LH 1,2; Li ZR 2; Xia YJ 3,4; Fraser NW 5; Gao F1; Zhou JM2; Li X2 ; Wang RL 2; Lang FC 2; gaofeng@jlu.edu.cn ; zhoujm@mail.kiz.ac.cn
	2016
发表期刊	JOURNAL OF NEUROVIROLOGY
卷号	22 期号:3 页码:293-306
合作性质	其它
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.
关键词	Treeshrew Hsv-1 Latency Reactivation Cns Explantcocultivation
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/10234
专题	科研部门_基因调控与表达遗传（周巨民）科研部门_动物模型与人类重大疾病机理重点实验室中国科学院昆明灵长类研究中心
通讯作者	gaofeng@jlu.edu.cn; zhoujm@mail.kiz.ac.cn
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
推荐引用方式 GB/T 7714	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*.,...&zhoujm@mail.kiz.ac.cn.(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.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2016070420.pdf（7813KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文