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Regulation of host and virus genes by neuronal miR-138 favours herpes simplex virus 1 latency.

ABSTRACT: MicroRNA miR-138, which is highly expressed in neurons, represses herpes simplex virus 1 (HSV-1) lytic cycle genes by targeting viral ICP0 messenger RNA, thereby promoting viral latency in mice. We found that overexpressed miR-138 also represses lytic processes independently of ICP0 in murine and human neuronal cells; therefore, we investigated whether miR-138 has targets besides ICP0. Using genome-wide RNA sequencing/photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation followed by short interfering RNA knockdown of candidate targets, we identified the host Oct-1 and Foxc1 messenger mRNAs as miR-138's targets, whose gene products are transcription factors important for HSV-1 replication in neuronal cells. OCT-1 has a known role in the initiation of HSV transcription. Overexpression of FOXC1, which was not known to affect HSV-1, promoted HSV-1 replication in murine neurons and ganglia. CRISPR-Cas9 knockout of FOXC1 reduced viral replication, lytic gene expression and miR-138 repression in murine neuronal cells. FOXC1 also collaborated with ICP0 to decrease heterochromatin on viral genes and compensated for the defect of an ICP0-null virus. In summary, miR-138 targets ICP0, Oct-1 and Foxc1 to repress HSV-1 lytic cycle genes and promote epigenetic gene silencing, which together enable favourable conditions for latent infection.

SUBMITTER: Sun B

PROVIDER: S-EPMC8221016 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Regulation of host and virus genes by neuronal miR-138 favours herpes simplex virus 1 latency.

Sun Boqiang B Yang Xuewei X Hou Fujun F Yu Xiaofeng X Wang Qiongyan Q Oh Hyung Suk HS Raja Priya P Pesola Jean M JM Vanni Emilia A H EAH McCarron Seamus S Morris-Love Jenna J Ng Alex H M AHM Church George M GM Knipe David M DM Coen Donald M DM Pan Dongli D

Nature microbiology 20210208 5

MicroRNA miR-138, which is highly expressed in neurons, represses herpes simplex virus 1 (HSV-1) lytic cycle genes by targeting viral ICP0 messenger RNA, thereby promoting viral latency in mice. We found that overexpressed miR-138 also represses lytic processes independently of ICP0 in murine and human neuronal cells; therefore, we investigated whether miR-138 has targets besides ICP0. Using genome-wide RNA sequencing/photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation ...[more]

PMID: 33558653

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Dataset Information

Regulation of host and virus genes by neuronal miR-138 favours herpes simplex virus 1 latency.

Publications

Regulation of host and virus genes by neuronal miR-138 favours herpes simplex virus 1 latency.

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