Herpes Simplex Virus 1 Infection of Tree Shrews Differs from That of Mice in the Severity of Acute Infection and Viral Transcription in the Peripheral Nervous System
文献类型：期刊论文
| 作者 | Li LH1; Li ZR1; Han HB2; Lang FC1; Li X1; Xia YJ3,4; Gao F5; Li QH6; Wang EL1; Fraser NW7 |
| 刊名 | JOURNAL OF VIROLOGY
 |
| 出版日期 | 2016 |
| 卷号 | 90期号:2页码:790-804 |
| 通讯作者 | zhoujm@mail.kiz.ac.cn |
| 英文摘要 | Studies of herpes simplex virus (HSV) infections of humans are limited by the use of rodent models such as mice, rabbits, and guinea pigs. Tree shrews (Tupaia belangeri chinensis) are small mammals indigenous to southwest Asia. At behavioral, anatomical, genomic, and evolutionary levels, tree shrews are much closer to primates than rodents are, and tree shrews are susceptible to HSV infection. Thus, we have studied herpes simplex virus 1 (HSV-1) infection in the tree shrew trigeminal ganglion (TG) following ocular inoculation. In situ hybridization, PCR, and quantitative reverse transcription-PCR (qRT-PCR) analyses confirm that HSV-1 latently infects neurons of the TG. When explant cocultivation of trigeminal ganglia was performed, the virus was recovered after 5 days of cocultivation with high efficiency. Swabbing the corneas of latently infected tree shrews revealed that tree shrews shed virus spontaneously at low frequencies. However, tree shrews differ significantly from mice in the expression of key HSV-1 genes, including ICP0, ICP4, and latency-associated transcript (LAT). In acutely infected tree shrew TGs, no level of ICP4 was observed, suggesting the absence of infection or a very weak, acute infection compared to that of the mouse. Immunofluorescence staining with ICP4 monoclonal antibody, and immunohistochemistry detection by HSV-1 polyclonal antibodies, showed a lack of viral proteins in tree shrew TGs during both acute and latent phases of infection. Cultivation of supernatant from homogenized, acutely infected TGs with RS1 cells also exhibited an absence of infectious HSV-1 from tree shrew TGs. We conclude that the tree shrew has an undetectable, or a much weaker, acute infection in the TGs. Interestingly, compared to mice, tree shrew TGs express high levels of ICP0 transcript in addition to LAT during latency. However, the ICP0 transcript remained nuclear, and no ICP0 protein could be seen during the course of mouse and tree shrew TG infections. Taken together, these observations suggest that the tree shrew TG infection differs significantly from the existing rodent models. IMPORTANCE Herpes simplex viruses (HSVs) establish lifelong infection in more than 80% of the human population, and their reactivation leads to oral and genital herpes. Currently, rodent models are the preferred models for latency studies. Rodents are distant from primates and may not fully represent human latency. The tree shrew is a small mammal, a prosimian primate, indigenous to southwest Asia. In an attempt to further develop the tree shrew as a useful model to study herpesvirus infection, we studied the establishment of latency and reactivation of HSV-1 in tree shrews following ocular inoculation. We found that the latent virus, which resides in the sensory neurons of the trigeminal ganglion, could be stress reactivated to produce infectious virus, following explant cocultivation and that spontaneous reactivation could be detected by cell culture of tears. Interestingly, the tree shrew model is quite different from the mouse model of HSV infection, in that the virus exhibited only a mild acute infection following inoculation with no detectable infectious virus from the sensory neurons. The mild infection may be more similar to human infection in that the sensory neurons continue to function after herpes reactivation and the affected skin tissue does not lose sensation. Our findings suggest that the tree shrew is a viable model to study HSV latency. |
| 收录类别 | SCI |
| 资助信息 | National Science Foundation of China provided funding to Jumin Zhou under grant number NSFC81471966. A Common Project of Panzhihua, Science and Technology Bureau of China provided funding to Hongbo Han under grant number 2012CY-S-22(9). A Visiting Professorship for Senior International Scientists from CAS provided funding to Nigel W. Fraserundergrantnumber2012T1S0001.KunmingInstituteofZoology, Chinese Academy of Sciences provided funding to Jumin Zhou under grant number Y102421081. Yunnan Provincial Government provided funding to Jumin Zhou under grant numbers 2011HA005 and 2013FA051. Chinese Academy of Sciences (CAS) provided funding to Jumin Zhou under grant number KSCXZ-EW-BR-6. This work was partially supported by the 863 Project (2012AA021801, 2012AA022402) from the Ministry of Science and Technology of China and by a one-three-five strategic planning project from the CAS. |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/10330]  |
| 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 |
| 作者单位 | 1.Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China 2.School of Life Sciences, Panzhihua College, Panzhihua, Sichuan, China 3.; Kunming Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China 4.Center for Drug Safety Evaluation, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China 5.; Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China 6.Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming, Kunming, China 7.Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA |
| 推荐引用方式 GB/T 7714 | Li LH,Li ZR,Han HB,et al. Herpes Simplex Virus 1 Infection of Tree Shrews Differs from That of Mice in the Severity of Acute Infection and Viral Transcription in the Peripheral Nervous System[J]. JOURNAL OF VIROLOGY,2016,90(2):790-804. |
| APA | Li LH.,Li ZR.,Han HB.,Lang FC.,Li X.,...&Xiao Y.(2016).Herpes Simplex Virus 1 Infection of Tree Shrews Differs from That of Mice in the Severity of Acute Infection and Viral Transcription in the Peripheral Nervous System.JOURNAL OF VIROLOGY,90(2),790-804. |
| MLA | Li LH,et al."Herpes Simplex Virus 1 Infection of Tree Shrews Differs from That of Mice in the Severity of Acute Infection and Viral Transcription in the Peripheral Nervous System".JOURNAL OF VIROLOGY 90.2(2016):790-804. |
入库方式： OAI收割
来源：昆明动物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。