A West Nile virus NS4B-P38G mutant strain induces cell intrinsic innate cytokine responses in human monocytic and macrophage cells |
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| Affiliation: | 1. Department of Microbiology & Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA;2. Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555, USA;3. Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA;4. Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77555, USA;5. Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, TX 77555 USA;1. HealthCore, Inc., 800 Delaware Avenue, Fifth Floor, Wilmington, DE 19801, United States;2. Department of Epidemiology, Merck Research Laboratories, 351 N. Sumneytown Pike, North Wales, PA 19454, United States;1. Department of Biological Structure, University of Washington School of Medicine, Seattle, WA 98195, USA;2. Elsa Biologics, LLC, Box 25725, WA 98165, USA;1. Department of Surgery, Emory University, Atlanta, Georgia;2. Department of Surgery, Duke University, Durham, North Carolina |
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| 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. |
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| Keywords: | West Nile virus NS4B protein Immune response Cytokine CNS" },{" #name" :" keyword" ," $" :{" id" :" kw0030" }," $$" :[{" #name" :" text" ," _" :" central nervous system DMEM" },{" #name" :" keyword" ," $" :{" id" :" kw0040" }," $$" :[{" #name" :" text" ," _" :" Dulbecco's modified eagle's medium E" },{" #name" :" keyword" ," $" :{" id" :" kw0050" }," $$" :[{" #name" :" text" ," _" :" envelope FBS" },{" #name" :" keyword" ," $" :{" id" :" kw0060" }," $$" :[{" #name" :" text" ," _" :" fetal bovine serum IFN" },{" #name" :" keyword" ," $" :{" id" :" kw0070" }," $$" :[{" #name" :" text" ," _" :" interferon IL" },{" #name" :" keyword" ," $" :{" id" :" kw0080" }," $$" :[{" #name" :" text" ," _" :" interleukin MOI" },{" #name" :" keyword" ," $" :{" id" :" kw0090" }," $$" :[{" #name" :" text" ," _" :" multiplicity of infection NFκB" },{" #name" :" keyword" ," $" :{" id" :" kw0100" }," $$" :[{" #name" :" text" ," _" :" nuclear factor kappa B PMA" },{" #name" :" keyword" ," $" :{" id" :" kw0110" }," $$" :[{" #name" :" text" ," _" :" phorbol 12-myristate 13-acetate Q-PCR" },{" #name" :" keyword" ," $" :{" id" :" kw0120" }," $$" :[{" #name" :" text" ," _" :" quantitative PCR RIG-I" },{" #name" :" keyword" ," $" :{" id" :" kw0130" }," $$" :[{" #name" :" text" ," _" :" retinoic acid inducible gene 1 TLR" },{" #name" :" keyword" ," $" :{" id" :" kw0140" }," $$" :[{" #name" :" text" ," _" :" toll-like receptor TNF-α" },{" #name" :" keyword" ," $" :{" id" :" kw0150" }," $$" :[{" #name" :" text" ," _" :" tumor necrosis factor α WNV" },{" #name" :" keyword" ," $" :{" id" :" kw0160" }," $$" :[{" #name" :" text" ," _" :" West Nile virus |
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