title: Wild-type rabies virus phosphoprotein is associated with viral sensitivity to type I interferon treatment.
abstract: Rabies virus (RABV) is a single-stranded, negative-sense RNA virus that causes a fatal neurological disease in humans and animals. Our previous studies have shown that lab-adapted, but not wild-type (wt), RABV enhances innate immune responses including type I interferon (IFN) and chemokines. To determine if treatment with type I IFN can inhibit RABV infection, mouse neuroblastoma and baby hamster kidney cells were treated with IFN-α before being infected with lab-adapted or wt RABV. It was found that lab-adapted, but not the wt, RABV was able to replicate in IFN-α-pretreated cells. To determine the genes in wt RABV that confer sensitivity to IFN-α treatment, the P and the glycoprotein (G) genes from the wt RABV were used to replace the respective genes in the lab-adapted RABV. The results revealed that it is the P, not the G, gene that is associated with IFN sensitivity. Further studies have identified the regions containing the self-association domain (residues 59-139) and the C-terminal (residue 175-297) region on the P that might be associated with IFN sensitivity. The expression of ISGs, such as ISG15, ISG56, PKR, OAS-1G, was also investigated and found to be greatly increased in wt, but not in lab-adapted RABV-infected cells. It is possible that the P protein from the lab-adapted RABV can interfere with the downstream events in the interferon-signaling cascade.
authors.affiliation: Department of Pathology, College of Veterinary Medicine, Athens, GA, 30602- 7388, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Niu
authors.forename: Lijun
authors.initials: L
authors.lastname: Tang
authors.forename: Tesfai
authors.initials: T
authors.lastname: Tseggai
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.forename: Zhen F
authors.initials: ZF
authors.lastname: Fu
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D007370:Interferon Type I / Q000276:immunology / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D018832:Molecular Chaperones; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011818:Rabies / Q000276:immunology* / Q000821:virology; D011820:Rabies virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D007370:Interferon Type I; D016898:Interferon-alpha; D018832:Molecular Chaperones; C103961:P phosphoprotein, Rabies virus; D010750:Phosphoproteins; D015678:Viral Structural Proteins