Longitudinal transcriptomic characterization of viral genes in HSV-1 infected tree shrew trigeminal ganglia

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Longitudinal transcriptomic characterization of viral genes in HSV-1 infected tree shrew trigeminal ganglia Erlin Wang1,4†, Yunshuang Ye1,4†, Ke Zhang2,8†, Jinlong Yang3,9†, Daohua Gong1,4, Jianhua Zhang5, Renjun Hong6, Huan Zhang6, Lihong Li1, Guijun Chen1, Liping Yang1, Jianmei Liu3, Hanyu Cao2, Ting Du2, Nigel W. Fraser7, Le Cheng3*, Xia Cao2* and Jumin Zhou1*

Abstract Background: Following acute infection, Herpes Simplex virus-1 (HSV-1) establishes lifelong latency and recurrent reactivation in the sensory neurons of trigeminal ganglia (TG). Infected tree shrew differs from mouse and show characteristics similar to human infection. A detailed transcriptomic analysis of the tree shrew model could provide mechanistic insights into HSV-1 infection in humans. Methods: We sequenced the transcriptome of infected TGs from tree shrews and mice, and 4 human donors, then examined viral genes expression up to 58 days in infected TGs from mouse and tree shrew, and compare the latency data with that in human TGs. Results: Here, we found that all HSV-1 genes could be detected in mouse TGs during acute infection, but 22 viral genes necessary for viral transcription, replication and viral maturation were not expressed in tree shrew TGs during this stage. Importantly, during latency, we found that LAT could be detected both in mouse and tree shrew, but the latter also has an ICP0 transcript signal absent in mouse but present in human samples. Importantly, we observed that infected human and tree shrew TGs have a more similar LAT region transcription peak. More importantly, we observed that HSV-1 spontaneously reactivates from latently infected tree shrews with relatively high efficiency. (Continued on next page)

* Correspondence: [email protected]; [email protected]; [email protected] † Erlin Wang, Yunshuang Ye, Ke Zhang and Jinlong Yang contributed equally to this work. 3 BGI-Yunnan, BGI-Shenzhen, Kunming 650000, Yunnan, China 2 Key Laboratory of Second Affiliated Hospital of Kunming Medical University, Kunming 650000, Yunnan, China 1 Key Laboratory of Animal Models and Human Disease Mechanism of the Chinese Academy of Science/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, Yunnan, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted