title: ICP4-induced miR-101 attenuates HSV-1 replication.
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.
authors.affiliation: 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.
authors.forename: Xiangling
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Diao
authors.affiliation: 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.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D017930:Genes, Reporter; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000378:metabolism*; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D039102:Poly(A)-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D020413:3' Untranslated Regions; C088356:GRSF1 protein, human; D017874:Immediate-Early Proteins; D035683:MicroRNAs; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D014764:Viral Proteins; C072628:herpes simplex virus IE3 protein, Human herpesvirus 1