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

Erlin Wang,Jianmei Liu,Ke Zhang,Liping Yang,Huan Zhang,Xia Cao,Nigel W Fraser,Renjun Hong,Yunshuang Ye,Le Cheng,Jumin Zhou,Guijun Chen,Daohua Gong,Hanyu Cao,Ting Du,Lihong Li,Jinlong Yang,Jianhua Zhang

doi:10.1186/s12985-020-01344-8

Abstract

BackgroundFollowing 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.MethodsWe 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.ResultsHere, 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.ConclusionsThese results represent the first longitudinal transcriptomic characterization of HSV-1 infection in during acute, latency and recurrent phases, and revealed that tree shrew infection has important similar features with human infection.

Highlights

Herpes simplex virus (HSV)-1 is a ubiquitous but important human pathogen carried by over half of the world’s population; Herpes Simplex virus-1 (HSV-1) infection starts with primary infection at the periphery and subsequent lifelong latency in the peripheral nervous system [1]
Viral infection dynamics vary among animal models To analyze the viral transcriptional patterns during acute and latent stages of HSV-1 infection, mice and tree shrews were infected with HSV-1 strain 17+ by corneal scarification, and infected trigeminal ganglia (TG) collected over a period of 58 days (Fig. 1a, b)
When using read count > 10 as the detection threshold of viral genes, we found that the number of viral genes were quite different between mice and tree shrews (Fig. 1c)

Summary

Introduction

HSV-1 is a ubiquitous but important human pathogen carried by over half of the world’s population; HSV-1 infection starts with primary infection at the periphery and subsequent lifelong latency in the peripheral nervous system [1]. In experimental animals such as mouse, acute infection develops following cornea inoculation, the virus replicates in the epithelial cells on the corneal surface and is later transported into trigeminal ganglia, where it establishes latency [2,3,4]. Herpes Simplex virus-1 (HSV-1) establishes lifelong latency and recurrent reactivation in the sensory neurons of trigeminal ganglia (TG). A detailed transcriptomic analysis of the tree shrew model could provide mechanistic insights into HSV-1 infection in humans

Methods

Results

Conclusion