CD11b maintains West Nile virus replication through modulation of immune response in human neuroblastoma cells.
CD11b
IFN
TNF-α
West Nile virus
Journal
Virology journal
ISSN: 1743-422X
Titre abrégé: Virol J
Pays: England
ID NLM: 101231645
Informations de publication
Date de publication:
14 Jul 2024
14 Jul 2024
Historique:
received:
12
03
2024
accepted:
03
07
2024
medline:
15
7
2024
pubmed:
15
7
2024
entrez:
14
7
2024
Statut:
epublish
Résumé
West Nile virus (WNV) is a rapidly spreading mosquito-borne virus accounted for neuroinvasive diseases. An insight into WNV-host factors interaction is necessary for development of therapeutic approaches against WNV infection. CD11b has key biological functions and been identified as a therapeutic target for several human diseases. The purpose of this study was to determine whether CD11b was implicated in WNV infection. SH-SY5Y cells with and without MEK1/2 inhibitor U0126 or AKT inhibitor MK-2206 treatment were infected with WNV. CD11b mRNA levels were assessed by real-time PCR. WNV replication and expression of stress (ATF6 and CHOP), pro-inflammatory (TNF-α), and antiviral (IFN-α, IFN-β, and IFN-γ) factors were evaluated in WNV-infected SH-SY5Y cells with CD11b siRNA transfection. Cell viability was determined by MTS assay. CD11b mRNA expression was remarkably up-regulated by WNV in a time-dependent manner. U0126 but not MK-2206 treatment reduced the CD11b induction by WNV. CD11b knockdown significantly decreased WNV replication and protected the infected cells. CD11b knockdown markedly increased TNF-α, IFN-α, IFN-β, and IFN-γ mRNA expression induced by WNV. ATF6 mRNA expression was reduced upon CD11b knockdown following WNV infection. These results demonstrate that CD11b is involved in maintaining WNV replication and modulating inflammatory as well as antiviral immune response, highlighting the potential of CD11b as a target for therapeutics for WNV infection.
Sections du résumé
BACKGROUND
BACKGROUND
West Nile virus (WNV) is a rapidly spreading mosquito-borne virus accounted for neuroinvasive diseases. An insight into WNV-host factors interaction is necessary for development of therapeutic approaches against WNV infection. CD11b has key biological functions and been identified as a therapeutic target for several human diseases. The purpose of this study was to determine whether CD11b was implicated in WNV infection.
METHODS
METHODS
SH-SY5Y cells with and without MEK1/2 inhibitor U0126 or AKT inhibitor MK-2206 treatment were infected with WNV. CD11b mRNA levels were assessed by real-time PCR. WNV replication and expression of stress (ATF6 and CHOP), pro-inflammatory (TNF-α), and antiviral (IFN-α, IFN-β, and IFN-γ) factors were evaluated in WNV-infected SH-SY5Y cells with CD11b siRNA transfection. Cell viability was determined by MTS assay.
RESULTS
RESULTS
CD11b mRNA expression was remarkably up-regulated by WNV in a time-dependent manner. U0126 but not MK-2206 treatment reduced the CD11b induction by WNV. CD11b knockdown significantly decreased WNV replication and protected the infected cells. CD11b knockdown markedly increased TNF-α, IFN-α, IFN-β, and IFN-γ mRNA expression induced by WNV. ATF6 mRNA expression was reduced upon CD11b knockdown following WNV infection.
CONCLUSION
CONCLUSIONS
These results demonstrate that CD11b is involved in maintaining WNV replication and modulating inflammatory as well as antiviral immune response, highlighting the potential of CD11b as a target for therapeutics for WNV infection.
Identifiants
pubmed: 39004752
doi: 10.1186/s12985-024-02427-6
pii: 10.1186/s12985-024-02427-6
doi:
Substances chimiques
CD11b Antigen
0
ITGAM protein, human
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
158Subventions
Organisme : National Key Research and Development Program of China
ID : 2016YFC1202903
Informations de copyright
© 2024. The Author(s).
Références
Lafri I, Hachid A, Bitam I. West Nile virus in Algeria: a comprehensive overview. New Microbes New Infect. 2018;27:9–13. https://doi.org/10.1016/j.nmni.2018.10.002 .
doi: 10.1016/j.nmni.2018.10.002
pubmed: 30519477
pmcid: 6260397
Suthar MS, Diamond MS, Gale M Jr. West Nile virus infection and immunity. Nat Rev Microbiol. 2013;11(2):115–28. https://doi.org/10.1038/nrmicro2950 .
doi: 10.1038/nrmicro2950
pubmed: 23321534
Byas AD, Ebel GD. Comparative pathology of West Nile virus in humans and non-human animals. Pathogens. 2020;9(1):48. https://doi.org/10.3390/pathogens9010048 .
doi: 10.3390/pathogens9010048
pubmed: 31935992
pmcid: 7168622
Rajaiah P, Mayilsamy M, Kumar A. West Nile virus in India: an update on its genetic lineages. J Vector Borne Dis. 2023;60(3):225–37. https://doi.org/10.4103/0972-9062.374039 .
doi: 10.4103/0972-9062.374039
pubmed: 37843232
Quicke KM, Suthar MS. The innate immune playbook for restricting West Nile virus infection. Viruses. 2013;5(11):2643–58. https://doi.org/10.3390/v5112643 .
doi: 10.3390/v5112643
pubmed: 24178712
pmcid: 3856407
Fulton CDM, Beasley DWC, Bente DA, Dineley KT. Long-term, West Nile virus-induced neurological changes: a comparison of patients and rodent models. Brain Behav Immun Health. 2020;7:100105. https://doi.org/10.1016/j.bbih.2020.100105 .
doi: 10.1016/j.bbih.2020.100105
pubmed: 34589866
pmcid: 8474605
Daffis S, Suthar MS, Gale M Jr, Diamond MS. Measure and countermeasure: type I IFN (IFN-alpha/beta) antiviral response against West Nile virus. J Innate Immun. 2009;1(5):435–45. https://doi.org/10.1159/000226248 .
doi: 10.1159/000226248
pubmed: 20375601
pmcid: 2920482
Zidovec-Lepej S, Vilibic-Cavlek T, Barbic L, Ilic M, Savic V, Tabain I, et al. Antiviral cytokine response in neuroinvasive and non-neuroinvasive West Nile virus infection. Viruses. 2021;13(2):342. https://doi.org/10.3390/v13020342 .
doi: 10.3390/v13020342
pubmed: 33671821
pmcid: 7927094
Schittenhelm L, Hilkens CM, Morrison VL. β2 integrins as regulators of dendritic cell, monocyte, and macrophage function. Front Immunol. 2017;8:1866. https://doi.org/10.3389/fimmu.2017.01866 .
doi: 10.3389/fimmu.2017.01866
pubmed: 29326724
pmcid: 5742326
Khan SQ, Khan I, Gupta V. CD11b activity modulates pathogenesis of lupus nephritis. Front Med (Lausanne). 2018;5:52. https://doi.org/10.3389/fmed.2018.00052 .
doi: 10.3389/fmed.2018.00052
pubmed: 29600248
Fagerholm SC, MacPherson M, James MJ, Sevier-Guy C, Lau CS. The CD11b-integrin (ITGAM) and systemic lupus erythematosus. Lupus. 2013;22(7):657–63. https://doi.org/10.1177/0961203313491851 .
doi: 10.1177/0961203313491851
pubmed: 23753600
Rosetti F, Mayadas TN. The many faces of Mac-1 in autoimmune disease. Immunol Rev. 2016;269(1):175–93. https://doi.org/10.1111/imr.12373 .
doi: 10.1111/imr.12373
pubmed: 26683153
Caiado F, Carvalho T, Rosa I, Remédio L, Costa A, Matos J, et al. Bone marrow-derived CD11b + Jagged2 + cells promote epithelial-to-mesenchymal transition and metastasization in colorectal cancer. Cancer Res. 2013;73(14):4233–46. https://doi.org/10.1158/0008-5472.CAN-13-0085 .
doi: 10.1158/0008-5472.CAN-13-0085
pubmed: 23722542
Lim SY, Gordon-Weeks A, Allen D, Kersemans V, Beech J, Smart S, et al. CD11b(+) myeloid cells support hepatic metastasis through down-regulation of angiopoietin-like 7 in cancer cells. Hepatology. 2015;62(2):521–33. https://doi.org/10.1002/hep.27838 .
doi: 10.1002/hep.27838
pubmed: 25854806
Hou L, Bao X, Zang C, Yang H, Sun F, Che Y, et al. Integrin CD11b mediates α-synuclein-induced activation of NADPH oxidase through a rho-dependent pathway. Redox Biol. 2018;14:600–8. https://doi.org/10.1016/j.redox.2017.11.010 .
doi: 10.1016/j.redox.2017.11.010
pubmed: 29154191
Stevanin M, Busso N, Chobaz V, Pigni M, Ghassem-Zadeh S, Zhang L, et al. CD11b regulates the Treg/Th17 balance in murine arthritis via IL-6. Eur J Immunol. 2017;47(4):637–45. https://doi.org/10.1002/eji.201646565 .
doi: 10.1002/eji.201646565
pubmed: 28191643
Saed GM, Fletcher NM, Diamond MP, Morris RT, Gomez-Lopez N, Memaj I. Novel expression of CD11b in epithelial ovarian cancer: potential therapeutic target. Gynecol Oncol. 2018;148(3):567–75. https://doi.org/10.1016/j.ygyno.2017.12.018 .
doi: 10.1016/j.ygyno.2017.12.018
pubmed: 29329880
Plow EF, Wang Y, Simon DI. The search for new antithrombotic mechanisms and therapies that may spare hemostasis. Blood. 2018;131(17):1899–902. https://doi.org/10.1182/blood-2017-10-784074 .
doi: 10.1182/blood-2017-10-784074
pubmed: 29467183
pmcid: 5921961
Tang WD, Tang HL, Peng HR, Ren RW, Zhao P, Zhao LJ. Inhibition of tick-borne encephalitis virus in cell cultures by Ribavirin. Front Microbiol. 2023;14:1182798. https://doi.org/10.3389/fmicb.2023.1182798 .
doi: 10.3389/fmicb.2023.1182798
pubmed: 37378295
pmcid: 10291047
Li SH, Li XF, Zhao H, Jiang T, Deng YQ, Yu XD, et al. Cross protection against lethal West Nile virus challenge in mice immunized with recombinant E protein domain III of Japanese encephalitis virus. Immunol Lett. 2011;138(2):156–60. https://doi.org/10.1016/j.imlet.2011.04.003 .
doi: 10.1016/j.imlet.2011.04.003
pubmed: 21515306
Clé M, Constant O, Barthelemy J, Desmetz C, Martin MF, Lapeyre L, et al. Differential neurovirulence of Usutu virus lineages in mice and neuronal cells. J Neuroinflammation. 2021;18(1):11. https://doi.org/10.1186/s12974-020-02060-4 .
doi: 10.1186/s12974-020-02060-4
pubmed: 33407600
pmcid: 7789689
Mundhra S, Bondre VP. Higher replication potential of West Nile virus governs apoptosis induction in human neuroblastoma cells. Apoptosis. 2023;28(7–8):1113–27. https://doi.org/10.1007/s10495-023-01844-2 .
doi: 10.1007/s10495-023-01844-2
pubmed: 37186273
Tang WD, Zhu WY, Tang HL, Zhao P, Zhao LJ. Engagement of AKT and ERK signaling pathways facilitates infection of human neuronal cells with West Nile virus. J Virus Erad. 2024;10(1):100368. https://doi.org/10.1016/j.jve.2024.100368 .
doi: 10.1016/j.jve.2024.100368
pubmed: 38601702
pmcid: 11004658
Srivastava R, Ramakrishna C, Cantin E. Anti-inflammatory activity of intravenous immunoglobulins protects against West Nile virus encephalitis. J Gen Virol. 2015;96(Pt 6):1347–57. https://doi.org/10.1099/vir.0.000079 .
doi: 10.1099/vir.0.000079
pubmed: 25667322
pmcid: 4635485
Getts DR, Terry RL, Getts MT, Müller M, Rana S, Shrestha B, et al. Ly6c+ inflammatory monocytes are microglial precursors recruited in a pathogenic manner in West Nile virus encephalitis. J Exp Med. 2008;205(10):2319–37. https://doi.org/10.1084/jem.20080421 .
doi: 10.1084/jem.20080421
pubmed: 18779347
pmcid: 2556789
Medigeshi GR, Lancaster AM, Hirsch AJ, Briese T, Lipkin WI, Defilippis V, et al. West Nile virus infection activates the unfolded protein response, leading to CHOP induction and apoptosis. J Virol. 2007;81(20):10849–60. https://doi.org/10.1128/JVI.01151-07 .
doi: 10.1128/JVI.01151-07
pubmed: 17686866
pmcid: 2045561
Ambrose RL, Mackenzie JM. ATF6 signaling is required for efficient West Nile virus replication by promoting cell survival and inhibition of innate immune responses. J Virol. 2013;87(4):2206–14. https://doi.org/10.1128/JVI.02097-12 .
doi: 10.1128/JVI.02097-12
pubmed: 23221566
pmcid: 3571479
Kumar M, Verma S, Nerurkar VR. Pro-inflammatory cytokines derived from West Nile virus (WNV)-infected SK-N-SH cells mediate neuroinflammatory markers and neuronal death. J Neuroinflammation. 2010;7:73. https://doi.org/10.1186/1742-2094-7-73 .
doi: 10.1186/1742-2094-7-73
pubmed: 21034511
pmcid: 2984415
Zhang B, Patel J, Croyle M, Diamond MS, Klein RS. TNF-alpha-dependent regulation of CXCR3 expression modulates neuronal survival during West Nile virus encephalitis. J Neuroimmunol. 2010;224(1–2):28–38. https://doi.org/10.1016/j.jneuroim.2010.05.003 .
doi: 10.1016/j.jneuroim.2010.05.003
pubmed: 20579746
pmcid: 2910216
Lee HJ, Zhao Y, Fleming I, Mehta S, Wang X, Wyk BV, et al. Early cellular and molecular signatures correlate with severity of West Nile virus infection. iScience. 2023;26(12):108387. https://doi.org/10.1016/j.isci.2023.108387 .
doi: 10.1016/j.isci.2023.108387
pubmed: 38047068
pmcid: 10692672
Nelson J, Ochoa L, Villareal P, Dunn T, Wu P, Vargas G, et al. Powassan virus induces structural changes in human neuronal cells in vitro and murine neurons in vivo. Pathogens. 2022;11(10):1218. https://doi.org/10.3390/pathogens11101218 .
doi: 10.3390/pathogens11101218
pubmed: 36297275
pmcid: 9609669
Shrestha B, Zhang B, Purtha WE, Klein RS, Diamond MS. Tumor necrosis factor alpha protects against lethal West Nile virus infection by promoting trafficking of mononuclear leukocytes into the central nervous system. J Virol. 2008;82(18):8956–64. https://doi.org/10.1128/JVI.01118-08 .
doi: 10.1128/JVI.01118-08
pubmed: 18632856
pmcid: 2546880
Kovats S, Turner S, Simmons A, Powe T, Chakravarty E, Alberola-Ila J. West Nile virus-infected human dendritic cells fail to fully activate invariant natural killer T cells. Clin Exp Immunol. 2016;186(2):214–26. https://doi.org/10.1111/cei.12850 .
doi: 10.1111/cei.12850
pubmed: 27513522
pmcid: 5054575
Hoover LI, Fredericksen BL. IFN-dependent and -independent reduction in West Nile virus infectivity in human dermal fibroblasts. Viruses. 2014;6(3):1424–41. https://doi.org/10.3390/v6031424 .
doi: 10.3390/v6031424
pubmed: 24662674
pmcid: 3970159
Takamatsu Y, Uchida L, Morita K. Delayed IFN response differentiates replication of West Nile virus and Japanese encephalitis virus in human neuroblastoma and glioblastoma cells. J Gen Virol. 2015;96(8):2194–9. https://doi.org/10.1099/vir.0.000168 .
doi: 10.1099/vir.0.000168
pubmed: 25920530