Abstract
HSV-1 infection in the cornea could lead to blindness. The infected cell polypeptide 4 (ICP4) of herpes simplex virus 1 (HSV-1) is a regulator of viral transcription that is required for productive infection. It has been previously demonstrated that miR-H6 encoded from HSV-1 genome targets ICP4 to help maintain latency. In this study, synthesized miR-H6 mimics were transfected into HSV-1-infected human cornea epithelial (HCE) cells. The inhibition of HSV-1 replication and viral ICP4 expression in miR-H6-transfected HCE was confirmed by plaque assay, immunofluorescence, and Western blot. Compared to nontransfection or mock, miR-H6 produced a low-titer HSV-1 and weak ICP4 expression. In addition, miR-H6 can decrease the interleukin 6 released into the medium, which was determined by ELISA. Taken together, the data suggests that miR-H6 targeting of ICP4 inhibits HSV-1 productive infection and decreases interleukin 6 production in HCE, and this may provide an approach to prevent HSV-1 lytic infection and inhibit corneal inflammation.
Highlights
Herpes simplex virus type 1 (HSV-1) is a linear doublestranded DNA virus that mainly infects epithelial and neuronal cells
During HSV-1 lytic infection, infected cell polypeptide 4 (ICP4) upregulates the early and late genes, downregulates the IE genes through interaction with the transcription factors associated with RNA polymerase II, and represses the latency-associated transcripts (LATs) promoter and prevents LAT production [36, 37]
We began this study with the goal of observing the effect of miR-H6 on HSV-1 replication and the inflammatory cytokine IL-6 production in human cornea epithelial (HCE), by which HSV-1 infections can lead to cornea blindness [21, 38]
Summary
Herpes simplex virus type 1 (HSV-1) is a linear doublestranded DNA virus that mainly infects epithelial and neuronal cells. MiR-H6 expression was significantly reduced in cells infected with a mutant HSV-2 virus with an insertion of a sequence between the LAT promoter and miR-H6 [18], and in latently, but not in acutely, infected mouse ganglia with HSV-1 LAT deletion mutants (dlLAT1.8) [17] These results suggested that when miR-H6 is expressed abundantly during lytic infection, it may play other roles during viral infection besides establishing and maintaining the latent infection [12, 17]. Regarding the abundant expression in lytic infection and the location of miR-H6 encoding sequence (upstream of LAT promoter), we wonder whether miR-H6 has different functions compared to other miRNAs (miR-H2-miR-H5) in HSV-1 infection. We found that miR-H6 targeting of ICP4 suppresses HSV-1 replication and decreases IL-6 production in HCE, and this may provide an approach to prevent HSV-1 lytic infection and inhibit inflammation in cornea
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