1887

Abstract

Rabies is a zoonotic disease caused by the rabies virus (RABV). RABV can lead to fatal encephalitis and is still a serious threat in most parts of the world. Interferon regulatory factor 7 (IRF7) is the main transcriptional regulator of type I IFN, and it is crucial for the induction of IFNα/β and the type I IFN-dependent immune response. In this study, we focused on the role of IRF7 in the pathogenicity and immunogenicity of RABV using an IRF7 mouse model. The results showed that the absence of IRF7 made mice more susceptible to RABV, because IRF7 restricted the replication of RABV in the early stage of infection. IRF7 deficiency affected the recruitment of plasmacytoid dendritic cells to the draining lymph nodes (dLNs), reduced the production of type I IFN and expression of IFN-stimulated genes. Furthermore, we found that the ability to produce specific RABV-neutralizing antibody was impaired in IRF7 mice. Consistently, IRF7 deficiency affected the recruitment of germinal-centre B cells to dLNs, and the generation of plasma cells and RABV-specific antibody secreting cells. Moreover, the absence of IRF7 downregulated the induction of IFN-γ and reduced type 1 T helper cell (Th1)-dependent antibody production. Collectively, our findings demonstrate that IRF7 promotes humoral immune responses and compromises the pathogenicity of RABV in a mouse model.

Funding
This study was supported by the:
  • national natural science foundation of china (Award 31522057 and 31872451)
    • Principle Award Recipient: LingZhao
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001665
2021-10-18
2024-05-12
Loading full text...

Full text loading...

References

  1. Schnell MJ, McGettigan JP, Wirblich C, Papaneri A. The cell biology of rabies virus: using stealth to reach the brain. Nat Rev Microbiol 2010; 8:51–61 [View Article] [PubMed]
    [Google Scholar]
  2. Shwiff S, Hampson K, Anderson A. Potential economic benefits of eliminating canine rabies. Antiviral Res 2013; 98:352–356 [View Article] [PubMed]
    [Google Scholar]
  3. Matsumoto S. Electron microscopy of nerve cells infected with street rabies virus. Virology 1962; 17:198–202198-&amp [View Article] [PubMed]
    [Google Scholar]
  4. Conzelmann KK, Cox JH, Schneider LG, Thiel HJ. Molecular-cloning and complete nucleotide-sequence of the attenuated rabies virus sad-B19. Virology 1990; 175:485–499 [View Article] [PubMed]
    [Google Scholar]
  5. Laothamatas J, Wacharapluesadee S, Lumlertdacha B, Ampawong S, Tepsumethanon V. Furious and paralytic rabies of canine origin: Neuroimaging with virological and cytokine studies. J Neurovirol 2008; 14:119–129 [View Article] [PubMed]
    [Google Scholar]
  6. Warrell DA. The clinical picture of rabies in man. Trans R Soc Trop Med Hyg 1976; 70:188–195 [View Article] [PubMed]
    [Google Scholar]
  7. Zhang L, Pagano JS. Structure and function of IRF-7. J Interferon Cytokine Res 2002; 22:95–101 [View Article] [PubMed]
    [Google Scholar]
  8. Marie I, Durbin JE, Levy DE. Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7. Embo J 1998; 17:6660–6669 [View Article] [PubMed]
    [Google Scholar]
  9. McNab F, Mayer-Barber K, Sher A, Wack A. Type I interferons in infectious disease. Nat Rev Immunol 2015; 15:87–103 [View Article] [PubMed]
    [Google Scholar]
  10. Uehata T, Takeuchi O. RNA recognition and immunity-innate immune sensing and its posttranscriptional regulation mechanisms. Cells 2020; 9: [View Article] [PubMed]
    [Google Scholar]
  11. Han H, Huang W, Du W, Shen Q, Yang Z. Involvement of interferon regulatory factor 7 in Nicotine’s suppression of antiviral immune responses. J Neuroimmune Pharmacol 2019; 14:551–564 [View Article] [PubMed]
    [Google Scholar]
  12. Ling T, Weng GX, Li J, Li C, Wang W. TARBP2 inhibits IRF7 activation by suppressing TRAF6-mediated K63-linked ubiquitination of IRF7. Mol Immunol 2019; 109:116–125 [View Article] [PubMed]
    [Google Scholar]
  13. Daffis S, Samuel MA, Suthar MS, Keller BC, Gale M. Interferon regulatory factor IRF-7 induces the antiviral alpha interferon response and protects against lethal West Nile virus infection. J Virol 2008; 82:8465–8475 [View Article] [PubMed]
    [Google Scholar]
  14. Honda K, Yanai H, Negishi H, Asagiri M, Sato M. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 2005; 434:772–777 [View Article] [PubMed]
    [Google Scholar]
  15. Chen HW, King K, Tu J, Sanchez M, Luster AD. The roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus. J Immunol 2013; 191:4194–4201 [View Article] [PubMed]
    [Google Scholar]
  16. Ciancanelli MJ, Abel L, Zhang SY, Casanova JL. Host genetics of severe influenza: from mouse Mx1 to human IRF7. Curr Opin Immunol 2016; 38:109–120 [View Article] [PubMed]
    [Google Scholar]
  17. Luo ZC, Lv L, Li YY, Sui BK, Wu Q et al. Dual role of toll-like receptor 7 in the pathogenesis of Rabies virus in a mouse model. J Virol 2020; 94:
    [Google Scholar]
  18. Luo Z, Li Y, Zhou M, Lv L, Wu Q. Toll-like receptor 7 enhances rabies virus-induced humoral immunity by facilitating the formation of germinal centers. Front Immunol 2019; 10:429 [View Article] [PubMed]
    [Google Scholar]
  19. Wen Y, Wang H, Wu H, Yang F, Tripp RA. Rabies virus expressing dendritic cell-activating molecules enhances the innate and adaptive immune response to vaccination. J Virol 2011; 85:1634–1644 [View Article] [PubMed]
    [Google Scholar]
  20. Sui B, Chen D, Liu W, Wu Q, Tian B. A novel antiviral lncRNA, EDAL, shields a T309 O-GlcNAcylation site to promote EZH2 lysosomal degradation. Genome Biol 2020; 21:228 [View Article] [PubMed]
    [Google Scholar]
  21. Reed LJ, Muench H. A simple method of estimating fifty per cent endpoints. Am J Epidemiol 1938; 27:493–497 [View Article]
    [Google Scholar]
  22. Li Y, Zhou M, Luo Z, Zhang Y, Cui M. Overexpression of Interleukin-7 Extends the Humoral Immune Response Induced by Rabies Vaccination. J Virol 2017; 91: [View Article] [PubMed]
    [Google Scholar]
  23. Zhang YC, Wu Q, Zhou M, Luo ZC, Lv L et al. Composition of the murine gut microbiome impacts humoral immunity induced by rabies vaccines. Clinical and Translational Medicine 2020; 10:
    [Google Scholar]
  24. Genin P, Lin RT, Hiscott J, Civas A. Differential regulation of human interferon A gene expression by interferon regulatory factors 3 and 7. Mol Cell Biol 2009; 29:3435–3450 [View Article] [PubMed]
    [Google Scholar]
  25. Bielekova B. Daclizumab therapy for multiple sclerosis. Cold Spring Harb Perspect Med 2019; 9: [View Article] [PubMed]
    [Google Scholar]
  26. Yang Y, Huang Y, Gnanadurai CW, Cao SB, Liu XQ. The inability of wild-type rabies virus to activate dendritic cells is dependent on the glycoprotein and correlates with its low level of the de novo-synthesized leader RNA. J Virol 2015; 89:2157–2169 [View Article] [PubMed]
    [Google Scholar]
  27. Ning S, Pagano JS, Barber GN. IRF7: activation, regulation, modification and function. Genes Immun 2011; 12:399–414 [View Article] [PubMed]
    [Google Scholar]
  28. Honda K, Taniguchi T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol 2006; 6:644–658 [View Article] [PubMed]
    [Google Scholar]
  29. Shah HB, Smith K, Wren JD, Webb CF, Ballard JD. Insights from analysis of human antigen-specific memory B cell repertoires. Front Immunol 2018; 9:3064 [View Article] [PubMed]
    [Google Scholar]
  30. Schoeler K, Aufschnaiter A, Messner S, Derudder E, Herzog S. TET enzymes control antibody production and shape the mutational landscape in germinal centre B cells. FEBS J 2019; 286:3566–3581 [View Article] [PubMed]
    [Google Scholar]
  31. Bastola R, Seo JE, Noh G, Keum T, Kim JH. Determination of Mycoplasma hyopneumoniae-specific IgG, IgG1, and IgG2a titers in BALB/c mice induced by mineral oil-based oil-in-water emulsion adjuvants prepared using a self-emulsifying drug delivery system. AAPS PharmSciTech 2019; 20:31 [View Article] [PubMed]
    [Google Scholar]
  32. Fan Y, Ma X, Ma L, Zhang J, Zhang W. Antioxidative and immunological activities of ophiopogon polysaccharide liposome from the root of Ophiopogon japonicus. Carbohydr Polym 2016; 135:110–120 [View Article] [PubMed]
    [Google Scholar]
  33. Randall RE, Goodbourn S. Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol 2008; 89:1–47 [View Article] [PubMed]
    [Google Scholar]
  34. Burbano C, Rojas M, Vásquez G, Castaño D. Microparticles that form immune complexes as modulatory structures in autoimmune responses. Mediators Inflamm 2015; 2015:267590 [View Article] [PubMed]
    [Google Scholar]
  35. Hu F, Wang H, Zhang S, Peng Y, Su L et al. Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester) ester nanovector induces donor-specific liver allograft tolerance. Int J Nanomedicine 2015; 10:4367–4382 [View Article] [PubMed]
    [Google Scholar]
  36. Cook LE, Locke MC, Young AR, Monte K, Hedberg ML et al. Distinct roles of interferon alpha and beta in controlling chikungunya virus replication and modulating neutrophil-mediated inflammation. J Virol 2020; 94:
    [Google Scholar]
  37. Fooks AR, Cliquet F, Finke S, Freuling C, Hemachudha T. Rabies. Nat Rev Dis Primers 2017; 3:17091 [View Article] [PubMed]
    [Google Scholar]
  38. Chopy D, Detje CN, Lafage M, Kalinke U, Lafon M. The type I interferon response bridles rabies virus infection and reduces pathogenicity. J Neurovirol 2011; 17:353–367 [View Article] [PubMed]
    [Google Scholar]
  39. Sato M, Suemori H, Hata N, Asagiri M, Ogasawara K. Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction. Immunity 2000; 13:539–548 [View Article] [PubMed]
    [Google Scholar]
  40. Becker Y. Immunological and regulatory functions of uninfected and virus infected immature and mature subtypes of dendritic cells--a review. Virus Genes 2003; 26:119–130 [View Article] [PubMed]
    [Google Scholar]
  41. Naze F, Suin V, Lamoral S, Francart A, Brochier B. Infectivity of rabies virus-exposed macrophages. Microbes Infect 2013; 15:115–125 [View Article] [PubMed]
    [Google Scholar]
  42. Li J, McGettigan JP, Faber M, Schnell MJ, Dietzschold B. Infection of monocytes or immature dendritic cells (DCs) with an attenuated rabies virus results in DC maturation and a strong activation of the NFkappaB signaling pathway. Vaccine 2008; 26:419–426 [View Article] [PubMed]
    [Google Scholar]
  43. Faul EJ, Wanjalla CN, Suthar MS, Gale M, Wirblich C. Rabies virus infection induces type I interferon production in an IPS-1 dependent manner while dendritic cell activation relies on IFNAR signaling. Plos Pathog 2010; 6:e1001016 [View Article] [PubMed]
    [Google Scholar]
  44. Jiang XZ, Shen CX, Rey-Ladino J, Yu H, Brunham RC. Characterization of murine dendritic cell line JAWS II and primary bone marrow-derived dendritic cells in Chlamydia muridarum antigen presentation and induction of protective immunity. Infect Immun 2008; 76:2392–2401 [View Article] [PubMed]
    [Google Scholar]
  45. Zhang Y, Zhou Z-W, Jin H, Hu C, He Z-X et al. Schisandrin B inhibits cell growth and induces cellular apoptosis and autophagy in mouse hepatocytes and macrophages: implications for its hepatotoxicity. Drug Des Devel Ther 2015; 9:2001–2027 [View Article] [PubMed]
    [Google Scholar]
  46. Lopez CB, Fernandez-Sesma A, Czelusniak SM, Schulman JL, Moran TM. A mouse model for immunization with ex vivo virus-infected dendritic cells. Cell Immunol 2000; 206:107–115 [View Article] [PubMed]
    [Google Scholar]
  47. Sun L, Liu W, Zhang LJ. The Role of toll-like receptors in skin host defense, psoriasis, and atopic dermatitis. J Immunol Res 2019; 2019:1824624 [View Article] [PubMed]
    [Google Scholar]
  48. Blasius AL, Beutler B. Intracellular toll-like receptors. Immunity 2010; 32:305–315 [View Article] [PubMed]
    [Google Scholar]
  49. Zhang LJ, Sen GL, Ward NL, Johnston A, Chun K. Antimicrobial peptide LL37 and MAVS signaling drive interferon-β production by epidermal keratinocytes during skin injury. Immunity 2016; 45:119–130 [View Article] [PubMed]
    [Google Scholar]
  50. Poeck H, Wagner M, Battiany J, Rothenfusser S, Wellisch D. Plasmacytoid dendritic cells, antigen, and CpG-C license human B cells for plasma cell differentiation and immunoglobulin production in the absence of T-cell help. Blood 2004; 103:3058–3064 [View Article] [PubMed]
    [Google Scholar]
  51. Macedo C, Hadi K, Walters J, Elinoff B, Marrari M. Impact of induction therapy on circulating T follicular helper cells and subsequent donor-specific antibody formation after kidney transplant. Kidney Int Rep 2019; 4:455–469 [View Article] [PubMed]
    [Google Scholar]
  52. Clingan JM, Matloubian M. B Cell-intrinsic TLR7 signaling is required for optimal B cell responses during chronic viral infection. J Immunol 2013; 191:810–818 [View Article] [PubMed]
    [Google Scholar]
  53. Gomme EA, Faul EJ, Flomenberg P, McGettigan JP, Schnell MJ. Characterization of a single-cycle rabies virus-based vaccine vector. J Virol 2010; 84:2820–2831 [View Article] [PubMed]
    [Google Scholar]
  54. Jegerlehner A, Maurer P, Bessa J, Hinton HJ, Kopf M et al. Tlr9 signaling in b cells determines class switch recombination to Igg2a. Swiss Med Wkly 2007; 137:22s
    [Google Scholar]
  55. Yendo AC, de Costa F, Cibulski SP, Teixeira TF, Colling LC. A rabies vaccine adjuvanted with saponins from leaves of the soap tree (Quillaja brasiliensis) induces specific immune responses and protects against lethal challenge. Vaccine 2016; 34:2305–2311 [View Article] [PubMed]
    [Google Scholar]
  56. Taylor JJ, Pape KA, Steach HR, Jenkins MK. Apoptosis and antigen affinity limit effector cell differentiation of a single naive B cell. Science 2015; 347:784–787 [View Article] [PubMed]
    [Google Scholar]
  57. Tjiam MC, Taylor JP, Morshidi MA, Sariputra L, Burrows S. Viremic HIV controllers exhibit high plasmacytoid dendritic cell-reactive opsonophagocytic IgG antibody responses against HIV-1 p24 associated with greater antibody isotype diversification. J Immunol 2015; 194:5320–5328 [View Article] [PubMed]
    [Google Scholar]
  58. Cruz LJ, Rueda F, Simon L, Cordobilla B, Albericio F. Liposomes containing NYESO1/tetanus toxoid and adjuvant peptides targeted to human dendritic cells via the Fc receptor for cancer vaccines. Nanomedicine (Lond) 2014; 9:435–449 [View Article] [PubMed]
    [Google Scholar]
  59. Lebrun A, Portocarrero C, Kean RB, Barkhouse DA, Faber M. T-bet is required for the rapid clearance of attenuated rabies virus from central nervous system tissue. J Immunol 2015; 195:4358–4368 [View Article] [PubMed]
    [Google Scholar]
  60. Agnello D, Lankford CSR, Bream J, Morinobu A, Gadina M. Cytokines and transcription factors that regulate T helper cell differentiation: New players and new insights. J Clin Immunol 2003; 23:147–161 [View Article] [PubMed]
    [Google Scholar]
  61. Deng YN, Bellanti JA, Zheng SG. Essential kinases and transcriptional regulators and their roles in autoimmunity. Biomolecules 2019; 9: [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001665
Loading
/content/journal/jgv/10.1099/jgv.0.001665
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error