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Volume 34 Issue 4
August 2019
    Citation: Rongquan Huang, Xusha Zhou, Shuqi Ren, Xianjie Liu, Zhiyuan Han, Grace Guoying Zhou. Effect of Loss-of-function of the Herpes Simplex Virus-1 microRNA H6-5p on Virus Replication .VIROLOGICA SINICA, 2019, 34(4) : 386-396.  http://dx.doi.org/10.1007/s12250-019-00111-6
    shu

    Effect of Loss-of-function of the Herpes Simplex Virus-1 microRNA H6-5p on Virus Replication

    cstr: 32224.14.s12250-019-00111-6
    • 1.

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

    • 2.

      Shenzhen International Institute for Biomedical Research, Shenzhen 518116, China

    • Corresponding author: Zhiyuan Han, zac_zhiyuan0420@126.com, ORCID: 0000-0001-6188-0433
      Grace Guoying Zhou, zhoug@siitm.org.cn, ORCID: 0000-0001-6188-0433
    • Rongquan Huang and Xusha Zhou contributed equally to this work.
      Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12250-019-00111-6) contains supplementary material, which is available to authorized users
    • Received Date: 07 December 2018
      Accepted Date: 28 February 2019
      Published Date: 24 April 2019
      Available online: 01 August 2019
    • To date, 29 distinct microRNAs (miRNAs) have been reported to be expressed during herpes simplex virus infections. Sequence analysis of mature herpes simplex virus-1 (HSV-1) miRNAs revealed five sets of miRNAs that are complementary to each other: miR-H6-5p/H1-3p, miR-H6-3p/H1-5p, H2-5p/H14-3p, miR-H2-3p/H14-5p, and miR-H7/H27. However, the roles of individual miRNAs and consequences of this complementarity remain unclear. Here, we focus on two of these complementary miRNAs, miR-H6-5p and miR-H1-3p, using loss-of-function experiments in vitro and in a mouse model of infection using an miRNA sponge approach, including tandem multiplex artificial miRNA-binding sequences that do not match perfectly to the target miRNA inserted downstream of a green fluorescent protein reporter gene. Infection with recombinant virus expressing the miR-H6-5p sponge reduced viral protein levels and virus yield. Decreased accumulation of viral proteins was also observed at early stages of infection in the presence of both an miR-H6-5p inhibitor and plasmid-expressed miR-H1-3p. Moreover, establishment of latency and reactivation did not differ between the recombinant virus expressing the miR-H6-5p sponge and wild-type HSV-1. Taken together, these data suggest that miR-H6-5p has an as-yet-unidentified role in the early stages of viral infection, and its complement miR-H1-3p suppresses this role in later stages of infection. This report extends understanding of the roles of miRNAs in infection by herpes simplex viruses, supporting a model of infection in which the production of virus and its virulent effects are tightly controlled to maximize persistence in the host and population.
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    • Electronic Supplementary Material

      10.1007s12250-019-00111-6-ESM1.pdf

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      Effect of Loss-of-function of the Herpes Simplex Virus-1 microRNA H6-5p on Virus Replication

        Corresponding author: Zhiyuan Han, zac_zhiyuan0420@126.com
        Corresponding author: Grace Guoying Zhou, zhoug@siitm.org.cn
      • 1. School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China
      • 2. Shenzhen International Institute for Biomedical Research, Shenzhen 518116, China
      • Received Date: 07 December 2018
      • Accepted Date: 28 February 2019
      • Published Date: 24 April 2019

      Abstract: To date, 29 distinct microRNAs (miRNAs) have been reported to be expressed during herpes simplex virus infections. Sequence analysis of mature herpes simplex virus-1 (HSV-1) miRNAs revealed five sets of miRNAs that are complementary to each other: miR-H6-5p/H1-3p, miR-H6-3p/H1-5p, H2-5p/H14-3p, miR-H2-3p/H14-5p, and miR-H7/H27. However, the roles of individual miRNAs and consequences of this complementarity remain unclear. Here, we focus on two of these complementary miRNAs, miR-H6-5p and miR-H1-3p, using loss-of-function experiments in vitro and in a mouse model of infection using an miRNA sponge approach, including tandem multiplex artificial miRNA-binding sequences that do not match perfectly to the target miRNA inserted downstream of a green fluorescent protein reporter gene. Infection with recombinant virus expressing the miR-H6-5p sponge reduced viral protein levels and virus yield. Decreased accumulation of viral proteins was also observed at early stages of infection in the presence of both an miR-H6-5p inhibitor and plasmid-expressed miR-H1-3p. Moreover, establishment of latency and reactivation did not differ between the recombinant virus expressing the miR-H6-5p sponge and wild-type HSV-1. Taken together, these data suggest that miR-H6-5p has an as-yet-unidentified role in the early stages of viral infection, and its complement miR-H1-3p suppresses this role in later stages of infection. This report extends understanding of the roles of miRNAs in infection by herpes simplex viruses, supporting a model of infection in which the production of virus and its virulent effects are tightly controlled to maximize persistence in the host and population.

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