Termination of Transcription of LAT Increases the Amounts of ICP0 mRNA but Does Not Alter the Course of HSV-1 Infection
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RESEARCH ARTICLE
Termination of Transcription of LAT Increases the Amounts of ICP0 mRNA but Does Not Alter the Course of HSV-1 Infection in Latently Infected Murine Ganglia Haifang Jiang1 • Jiaming Wu1 • Xianjie Liu2 • Ruitao Lu1 • Manling Zhou1 • Meiling Chen1 • Yonghong Liu1 Grace Guoying Zhou2 • Wenmin Fu2
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Received: 20 May 2020 / Accepted: 31 July 2020 Ó Wuhan Institute of Virology, CAS 2020
Abstract On entering sensory ganglia, herpes simplex viruses 1 (HSV-1) establishes a latent infection with the synthesis of a latency associated transcript (LAT) or initiates productive infection with expression of a set of immediate early viral proteins. The precise mechanisms how expression of a genes is suppressed during the latency are unknown. One mechanism that has been proposed is illustrated in the case of ICP0, a key immediate early viral regulatory protein. Specifically, the 2 kb LAT intron is complementary to the 30 terminal portion of ICP0 mRNA. To test the hypothesis that accumulation of LAT negatively affects the accumulation of ICP0 mRNA, we inserted a DNA fragment encoding two poly(A) sequences into LAT to early terminate LAT transcript without interrupting the complementary sequence of ICP0 transcript (named as SR1603). Comparisons of the parent (SR1601) and mutant (SR1603) HSV-1 viruses showed the following: Neurons harboring latent SR1603 virus accumulated equivalent amounts of viral DNA but higher amounts of ICP0 mRNA and lower amounts of LAT, when compared to neurons harboring the SR1601 virus. One notable difference between the two viruses is that viral RNA accumulation in explanted ganglia harboring SR1603 virus initiated significantly sooner than that in neurons harboring SR1601 virus, suggesting that ICP0 may act as an activator of viral gene expression in permissive cells. Collectively, these data suggest that increased ICP0 mRNA by suppressed LAT did not affect the establishment of latency in latently infected murine ganglia. Keywords Herpes simplex viruses 1 (HSV-1) Latency associated transcript (LAT) ICP0 Latency
Introduction
Haifang Jiang and Jiaming Wu contributed equally.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12250-020-00287-2) contains supplementary material, which is available to authorized users. & Wenmin Fu [email protected] & Grace Guoying Zhou [email protected] 1
School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China
2
Shenzhen International Institute for Biomedical Research, Shenzhen 518116, China
A key characteristic of herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) is that once virus entry into the cells, viral DNA is transported to neurons of sensory ganglia in which they either express immediate early viral regulatory proteins to initiate viral lytic replication or express an 8.3–9 kb RNA designated as the latency associated transcript precursor (LAT-P) to establish a latent infection
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