Abstract
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.
Highlights
Host cells have evolved a variety of mechanisms to counteract viral infection, especially interferon (IFN)-dependent antiviral innate immunity
The involvement of miRNAs from host cells and/or Herpes simplex virus type 1 (HSV-1)-encoded miRNAs during viral infections in the regulation of the cytosolic DNA–stimulated type I IFN pathway was investigated by constructing a dual-luciferase reporter carrying a 30 -UTR of signaling protein mRNAs, which included cytosolic
Some others, such as TRIF and DAI reporter expression had a significant decrement only in THP-1 cells (Figure 1C,D). These results showed that DEAD-box helicase 41 (DDX41) reporter expression was inhibited significantly in a 30 -UTR-dependent manner during HSV-1 infection
Summary
Host cells have evolved a variety of mechanisms to counteract viral infection, especially interferon (IFN)-dependent antiviral innate immunity. Viruses 2019, 11, 756 an immediate early (IE, α) protein possessing an E3 ubiquitin ligase activity, expressing highly during lytic infection. It promotes the degradation of certain host proteins including alpha thalassemia/mental retardation syndrome X-linked (ATRX) [7], myeloid differentiation factor (MyD88), MyD88 adaptor–like protein (Mal), and Toll-interleukin 1 receptor (TIR) domain–containing adaptor protein (TIRAP) [8], P65 [9], IFI16 [10,11,12], and STING [13] to enhance viral infection and replication by abrogating type I IFN production and facilitating immune evasion [14]. Some other viral proteins such as UL36USP [20,21,22,23], US11 [24,25], ICP34.5 [26,27], US3 [28,29,30], ICP47 [31,32], ICP27 [33], and so on are proved to be involved in immune evasion by targeting correlative components of the antiviral immune pathway
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
