title: A West Nile virus NS4B-P38G mutant strain induces cell intrinsic innate cytokine responses in human monocytic and macrophage cells.
abstract: Previous studies have shown that an attenuated West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant induces stronger innate and adaptive immune responses than wild-type WNV in mice, which has important applications to vaccine development. To investigate the mechanism of immunogenicity, we characterized WNV NS4B-P38G mutant infection in two human cell lines-THP-1 cells and THP-1 macrophages. Although the NS4B-P38G mutant produced more viral RNA than the parental WNV NY99 in both cell types, there was no detectable infectious virus in the supernatant of either cell type. Nonetheless, the attenuated mutant boosted higher innate cytokine responses than virulent parental WNV NY99 in these cells. The NS4B-P38G mutant infection of THP-1 cells led to more diverse and robust innate cytokine responses than that seen in THP-1 macrophages, which were mediated by toll-like receptor (TLR)7 and retinoic acid-inducible gene 1(RIG-I) signaling pathways. Overall, these results suggest that a defective viral life cycle during NS4B-P38G mutant infection in human monocytic and macrophage cells leads to more potent cell intrinsic innate cytokine responses.
authors.affiliation: Department of Microbiology & Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Guorui
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Microbiology & Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Huanle
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Tian
authors.affiliation: Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Mann
authors.affiliation: Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Bao
authors.affiliation: Department of Microbiology & Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, TX 77555 USA.
authors.forename: Jere
authors.initials: J
authors.lastname: McBride
authors.affiliation: Department of Microbiology & Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, TX 77555 USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Tesh
authors.affiliation: Department of Microbiology & Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, TX 77555 USA.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Barrett
authors.affiliation: Department of Microbiology & Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, TX 77555 USA. Electronic address: ti1wang@utmb.edu.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014902:West Nile virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12
keywords: Cytokine; Immune response; NS4B protein; West Nile virus