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

Autor: Sun B; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China.; Department of Infectious Diseases of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Thermo Fisher Scientific, Shanghai, China., Yang X; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China.; Department of Infectious Diseases of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Innovent Biologics, Inc., Suzhou, China., Hou F; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China.; Department of Infectious Diseases of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China., Yu X; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China.; Department of Infectious Diseases of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Zhejiang Chinese Medical University, Hangzhou, China., Wang Q; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China.; Department of Infectious Diseases of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China., Oh HS; Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Raja P; Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Pesola JM; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Vanni EAH; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., McCarron S; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Morris-Love J; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.; Graduate Program in Pathobiology, Brown University, Providence, RI, USA., Ng AHM; Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA.; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Church GM; Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA.; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Knipe DM; Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Coen DM; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Pan D; Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China. pandongli@zju.edu.cn.; Department of Infectious Diseases of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. pandongli@zju.edu.cn.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2021 May; Vol. 6 (5), pp. 682-696. Date of Electronic Publication: 2021 Feb 08.
DOI: 10.1038/s41564-020-00860-1
Abstrakt: 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.
Databáze: MEDLINE
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