MiR-23a facilitates the replication of HSV-1 through the suppression of interferon regulatory factor 1
Authors: Hua Tang
Min Liu
Chunmei Wang
Huahui Sun
Jing Ru
Hongxia Fan
Yixuan Li
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: MicroRNAs; gene expression; herpes simplex virus type 1; replication; interferon regulatory factor 1
Affiliations: Tianjin Life Science Research Center and Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Department of Pathophysiology, School of Basic Medical Sciences, Yunnan University of Traditional Chinese Medicine, Kunming 650500, China., Tianjin Life Science Research Center and Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.

Abstract:  MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression. It has been reported that miRNAs are involved in host-virus interaction, but evidence that cellular miRNAs promote virus replication has been limited. Here, we found that miR-23a promoted the replication of human herpes simplex virus type 1 (HSV-1) in HeLa cells, as demonstrated by a plaque-formation assay and quantitative real-time PCR. Furthermore, interferon regulatory factor 1 (IRF1), an innate antiviral molecule, is targeted by miR-23a to facilitate viral replication. MiR-23a binds to the 3'UTR of IRF1 and down-regulates its expression. Suppression of IRF1 expression reduced RSAD2 gene expression, augmenting HSV-1 replication. Ectopic expression of IRF1 abrogated the promotion of HSV-1 replication induced by miR-23a. Notably, IRF1 contributes to innate antiviral immunity by binding to IRF-response elements to regulate the expression of interferon-stimulated genes (ISGs) and apoptosis, revealing a complex interaction between miR-23a and HSV-1. MiR-23a thus contributes to HSV-1 replication through the regulation of the IRF1-mediated antiviral signal pathway, which suggests that miR-23a may represent a promising target for antiviral treatments. 

Retracted: No

PubPeer comments:
 Figure 1F appears to have 2 images which overlap. Shown in green (brightness enhanced). ***  , 
 Figure 1F, DAPI Anti-miR-23A appears to show an overlap with Figure 3F, DAPI pSilencer. Shown in yellow. Updated with a finding by Still Sciencing on Twitter in pink.  , 
 Expression of Concern: MiR-23a Facilitates the Replication of HSV-1 through the Suppression of Interferon Regulatory Factor 1 The PLOS ONE Editors Following publication of this article [1], concerns were raised that the following panels appear to show overlapping data: Fig 1F, HSV-1 glycoprotein and DAPI panels for pcDNA3 and pRNAT-U6.2 Fig 1F, HSV-1 glycoprotein and DAPI panels for Anti-miR-23a (left portion) in Fig 1F and pSilencer (right portion) in Fig 3F  Fig 1. MiR-23a promotes the replication of HSV-1. (A) HeLa cells were transfected with Pri-miR-23a, pcDNA3, Anti-miR-23a and pRNAT-U6.2, respectively. At 24 h post-transfection, total RNA was extracted and analyzed for miR-23a expression by quantitative real-time PCR. (B) HeLa cells were transfected as indicated in (A). Cell viability was measured by MTT assay at 24 h, 48 h and 72 h post-transfection. To up-regulate miR-23a, two doses of vectors were used for transfection, 0.5 u03bcg well and 0.3 u03bcg well. Another group was transfected with Anti-miR-23a and its control vector in the same way. (Cu2013F) HeLa cells were transfected as indicated in (A), 24 h post-transfection, cells were infected with HSV-1 at 0.01 PFU cell. At 48 h post-infection, the radius of the cytopathic area was measured by neutral red staining. The scale bar represents 100 u03bcm (C). Total viral yields (D) and yield of progeny virions from the culture supernatant (E) were determined by standard plaque assays. Level of glycoprotein expression was determined by immunofluorescence assay (F). All data represent the mean value u00b1 SD of at least three independent experiments. *: p 0.05; **: p 0.01; ***: p 0.001; ns: No significant differences by Student s t test. doi:10.1371 journal.pone.0234092.g001 The authors noted that incorrect images are reported in Fig 1F for pRNAT-U6.2 and Anti-miR-23a, and that the correct image data are reported in Fig 3F. They provided an updated Fig 1 using the correct images from the original experiment, along with supporting image files for Figs 1F and 3F in S1 and S2 Files. In addition, the Data Availability statement for this article reads u201cAll relevant data are within the paper.u201d However, the primary data are not included with the article and the authors noted that except for the data in S1 and S2 Files the original data for this study are no longer available. As such, the article does not comply with PLOS ONEu2019s Data Availability policy that was in place at the time of the articleu2019s submission. In light of the above concerns, the PLOS ONE Editors issue this Expression of Concern. The Data Availability statement is updated to: Image data for Figs 1F and 3F are in the Supporting Information files of this notice [1]. The original data underlying other results reported in the article are no longer available. , 
 There also appears to be a small area of overlap in Figure 3F. There seems to be very little reason not to retract this very flawed paper. *** Closeup comparison  *** Full figure  ,