ICP4-induced miR-101 attenuates HSV-1 replication
Authors: Xin Li
Xiangling Wang
Zhen Yang
Hua Tang
Min Liu
Caifeng Diao
Xi Yang
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: HSV-1; miR-101; ICP4; GRSF1; host-virus interactions
Affiliations: Tianjin Life Science Research Center and Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin 300070, China.

Abstract:  Hepes simplex Virus type 1 (HSV-1) is an enveloped DNA virus that can cause lytic and latent infection. miRNAs post-transcriptionally regulate gene expression, and our previous work has indicated that HSV-1 infection induces miR-101 expression in HeLa cells. The present study demonstrates that HSV-1-induced miR-101 is mainly derived from its precursor hsa-mir-101-2, and the HSV-1 immediate early gene ICP4 (infected-cell polypeptide 4) directly binds to the hsa-mir-101-2 promoter to activate its expression. RNA-binding protein G-rich sequence factor 1 (GRSF1) was identified as a new target of miR-101; GRSF1 binds to HSV-1 p40 mRNA and enhances its expression, facilitating viral proliferation. Together, ICP4 induces miR-101 expression, which downregulates GRSF1 expression and attenuates the replication of HSV-1. This allows host cells to maintain a permissive environment for viral replication by preventing lytic cell death. These findings indicate that HSV-1 early gene expression modulates host miRNAs to regulate molecular defense mechanisms. This study provides novel insight into host-virus interactions in HSV-1 infection and may contribute to the development of antiviral therapeutics. 

Retracted: No

PubPeer comments:
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 There seems to also be a duplication of panels between Figure 5 Panel D and Figure 6 Panel E Figure 5 Panel D: ![file] Figure 6 Panel E (note that the same DAPI image appears twice): ![file] , 
 Dear Actinopolyspora Biskrensis and Nymphalis Xanthomelas, ![file] ![file] Thank you very much for pointing out this error. We checked the original data. During the preparation of figures submitted in the original manuscript, the authors inadvertently provided an incorrect image for Figure 5D and Figure 6E. We have corrected them. In Figure 5D, the three images of the pcDNA3 group were correctly combined, and the error occurred in the pSilencer-NC group, the correct images of the pSilencer-NC group are updated. In Figure 5D and Figure 6E, there both have pcDNA3 group cells, the same photo was wrongly placed by mistake, the correct group image has been updated for figure 6E. For DAPI images, DAPI image of pcDNA3 group is correct, DAPI image of pri-mir-101 + pGRSF1-FLAG group was incorrect, the correct image is updated. The corrected Figure 5D and 6E are provided below. The error did not affect the overall conclusions and we will make the corrigendum. We sincerely apologize for this mistake due to our carelessness. Yours sincerely, Xiangling Wang Hua Tang , 
 Have the authors contacted the journal in order to make this correction? , 
 Yes. The correction will come out. Thank you. , 
 Author Correction, Published: 06 August 2021 This Article contains errors in Figures 5 and 6. In panel D of Figure 5, the images Glycoprotein and Merge for pSilencer-NC are a duplication of the images Glycoprotein and Merge for pcDNA3. The correct Figure 5 appears below. ![file] In panel E of Figure 6, all images for pcDNA3 are a duplication of the corresponding pcDNA3 images in panel D of Figure 5. Additionally, the image DAPI for pri-mir-101u2009+u2009pGRSF1-FLAG is a duplication of the image DAPI for pcDNA3 in panel D of Figure 5. The correct Figure 6 appears below. ![file] , 
 I did not see that this paper was one of 31 papers discussed here: https: www.nsfc.gov.cn publish portal0 tab442 info85495.htm, however it appears that this author (among others) was investigated for suspected misconduct. March 30, 2022  Decision on the handling of problems such as improper manipulation of images, confusion of experimental data, and false information in project applications, progress reports and final reports published by Tang Hua et al. National Science and Technology Financial Supervisory Office [2022] No. 2 The Supervision Committee of the National Natural Science Foundation of China launched an investigation into the papers published by Tang Hua and others of Tianjin Medical University for suspected academic misconduct.... According to the investigation of the supporting unit, the above paper has problems such as improper operation of pictures and confusion of experimental data. The corresponding author Tang Hua is mainly responsible for the above problems.  ,