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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

  • Research Article
  • Published:
Virologica Sinica

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 α 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 3′ 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.

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Acknowledgements

These studies were supported by grants from Shenzhen Overseas High-Caliber Peacock Foundation KQTD2015071414385495, Shenzhen Science and Innovation Commission Project Grants JCYJ20180306173333907 to Shenzhen International Institute for Biomedical Research.

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Author notes

  1. Haifang Jiang and Jiaming Wu contributed equally.

Authors and Affiliations

  1. School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China

    Haifang Jiang, Jiaming Wu, Ruitao Lu, Manling Zhou, Meiling Chen & Yonghong Liu

  2. Shenzhen International Institute for Biomedical Research, Shenzhen, 518116, China

    Xianjie Liu, Grace Guoying Zhou & Wenmin Fu

Authors
  1. Haifang Jiang
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  2. Jiaming Wu
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  3. Xianjie Liu
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  4. Ruitao Lu
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  5. Manling Zhou
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  6. Meiling Chen
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  7. Yonghong Liu
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  8. Grace Guoying Zhou
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  9. Wenmin Fu
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Contributions

HJ, JW, XL, GZ, WF designed research; HJ, JW, XL, RL, MZ, MC, YL performed research; HJ, JW, GZ, WF analyzed data, GZ, WF wrote and finalized the paper. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Grace Guoying Zhou or Wenmin Fu.

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The authors declare no conflict of interests.

Animal and Human Rights Statement

All animal studies were done in accordance with guidelines and protocols approved by the Institutional Animal Care and Use Committee of the Shenzhen International Institute for Biomedical Research.

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Jiang, H., Wu, J., Liu, X. et al. 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. Virol. Sin. 36, 264–272 (2021). https://doi.org/10.1007/s12250-020-00287-2

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