title: Cellular protein GLTSCR2: A valuable target for the development of broad-spectrum antivirals.
abstract: Viral infection induces translocation of the nucleolar protein GLTSCR2 from the nucleus to the cytoplasm, resulting in attenuation of the type I interferon IFN-β. Addressing the role of GLTSCR2 in viral replication, we detect that knocking down GLTSCR2 by shRNAs results in significant suppression of viral replication in mammalian and chicken cells. Injection of chicken embryo with the GLTSCR2-specific shRNA-1370 simultaneously or 24 h prior to infection with Newcastle disease virus (NDV) substantially reduces viral replication in chicken embryo fibroblasts. Injection of shRNA-1370 into chicken embryo also reduces the replication of avian influenza virus (AIV). In contrast, GLTSCR2-derived protein G4-T, forming α-helical dimers, increases replication of seven various DNA and RNA viruses in cells. Our studies reveal that alteration of the function of cellular GLTSCR2 plays a role in supporting viral replication. GLTSCR2 should be seriously considered as a therapeutic target for developing broad spectrum antiviral agents to effectively control viral infection.
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Cui-Cui
authors.initials: CC
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Dong
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Meng
authors.affiliation: Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Chi
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Shi-Chong
authors.initials: SC
authors.lastname: Han
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Ning
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China. Electronic address: wangxj@cau.edu.cn.
authors.forename: Xiao-Jia
authors.initials: XJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D004267:DNA Viruses / Q000187:drug effects; D004285:Dogs; D005347:Fibroblasts / Q000821:virology; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000235:genetics; D007370:Interferon Type I / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D009521:Newcastle Disease / Q000821:virology; D009522:Newcastle disease virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000072756:Protein Conformation, alpha-Helical / Q000187:drug effects; D012328:RNA Viruses / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D007370:Interferon Type I; D016898:Interferon-alpha; C500712:NOP53 protein, human; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: DNA virus; GLTSCR2; RNA virus; Viral replication; shRNA