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Herpes Simplex Virus Type 1–Encoded miR-H2-3p Manipulates Cytosolic DNA–Stimulated Antiviral Innate Immune Response by Targeting DDX41

1
Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China
2
Experimental Center for Medical Research, Kunming Medical University, Kunming 650500, China
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(8), 756; https://doi.org/10.3390/v11080756
Received: 15 June 2019 / Revised: 28 July 2019 / Accepted: 6 August 2019 / Published: 15 August 2019
(This article belongs to the Section Animal Viruses)
Herpes simplex virus type 1 (HSV-1), one of the human pathogens widely epidemic and transmitted among various groups of people in the world, often causes symptoms known as oral herpes or lifelong asymptomatic infection. HSV-1 employs many sophisticated strategies to escape host antiviral immune response based on its multiple coding proteins. However, the functions involved in the immune evasion of miRNAs encoded by HSV-1 during lytic (productive) infection remain poorly studied. Dual-luciferase reporter gene assay and bioinformatics revealed that Asp-Glu-Ala-Asp (DEAD)-box helicase 41 (DDX41), a cytosolic DNA sensor of the DNA-sensing pathway, was a putative direct target gene of HSV-1-encoded miR-H2-3p. The transfection of miR-H2-3p mimics inhibited the expression of DDX41 at the level of mRNA and protein, as well as the expression of interferon beta (IFN-β) and myxoma resistance protein I (MxI) induced by HSV-1 infection in THP-1 cells, and promoted the viral replication and its gene transcription. However, the transfection of miR-H2-3p inhibitor showed opposite effects. This finding indicated that HSV-1-encoded miR-H2-3p attenuated cytosolic DNA–stimulated antiviral immune response by manipulating host DNA sensor molecular DDX41 to enhance virus replication in cultured cells. View Full-Text
Keywords: antiviral immune response; cytosolic DNA sensor; HSV-1; miR-H2-3p antiviral immune response; cytosolic DNA sensor; HSV-1; miR-H2-3p
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MDPI and ACS Style

Duan, Y.; Zeng, J.; Fan, S.; Liao, Y.; Feng, M.; Wang, L.; Zhang, Y.; Li, Q. Herpes Simplex Virus Type 1–Encoded miR-H2-3p Manipulates Cytosolic DNA–Stimulated Antiviral Innate Immune Response by Targeting DDX41. Viruses 2019, 11, 756.

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