Abstract
Simian varicella virus (SVV) infection of non-human primates models human varicella zoster virus (VZV) infection. Assessment of cell signaling immune responses in monkeys after primary SVV infection, after immunosuppression and during reactivation revealed strong pro-inflammatory responses and lesser anti-inflammatory components during varicella and reactivation. Pro-inflammatory mediators elevated during varicella included interferon-gamma (IFN-γ), interleukin (IL)-6, monocyte chemoattractant protein (MCP-1), interferon inducible T-cell α chemoattractant protein (I-TAC), interferon processing protein (IP-10), and anti-inflammatory interleukin-1 Receptor antagonist (IL-1Ra). After immunosuppression and at reactivation, levels of pro-inflammatory mediators MCP-1, eotaxin, IL-6, IL-8, MIF, RANTES (regulated-on-activation normal T-cell expressed and secreted), and HGF (hepatocyte growth factor) were elevated, as was the anti-inflammatory mediator IL-1Ra. Characterization of cytokine, chemokine and growth factor responses during different stages of varicella virus infection will facilitate immunotherapeutic and vaccine strategies.
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References
Arend WP (1991) Interleukin 1 receptor antagonist. A new member of the interleukin 1 family. J Clin Invest 88:1445–1451
Arvin AM, Koropchak CM, Williams BR, Grumet FC, Foung SK (1986) Early immune response in healthy and immunocompromised subjects with primary varicella-zoster virus infection. J Infect Dis 154:422–429
Deshmane SL, Kremlev S, Amini S, Sawaya BE (2009) Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res 29:313–326
Dinarello CA (1991) Interleukin-1 and interleukin-1 antagonism. Blood 77:1627–1652
Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD (2002) IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol 168:3195–3204
James SF, Traina-Dorge V, Deharo E, Wellish M, Palmer BE, Gilden D (2014) Mahalingam R (2014) T cells increase before zoster and PD-1 expression increases at the time of zoster in immunosuppressed nonhuman primates latently infected with simian varicella virus. J Neurovirol 20:309–313
Li B, Xu W, Xu L, Jiang Z, Wen Z, Li K, Xiong S (2010) I-TAC is a dominant chemokine in controlling skin intragraft inflammation via recruiting CXCR3+ cells into the graft. Cell Immunol 260:83–91
Mahalingam R, Wellish M, Soike K, White T, Kleinschmidt-DeMasters BK, Gilden DH (2001) Simian varicella virus infects ganglia before rash in experimentally infected monkeys. Virology 279:339–342
Mahalingam R, Traina-Dorge V, Wellish M, Lorino R, Sanford R, Ribka EP, Alleman SJ, Brazeau E, Gilden DH (2007) Simian varicella virus reactivation in cynomolgus monkeys. Virology 368:50–59
Mahalingam R, Messaoudi I, Gilden D (2010a) Simian varicella virus pathogenesis. Curr Top Microbiol Immunol 342:309–321
Mahalingam R, Traina-Dorge V, Wellish M, Deharo E, Singletary ML, Ribka EP, Sanford R, Gilden D (2010b) Latent simian varicella virus reactivates in monkeys treated with tacrolimus with or without exposure to irradiation. J Neurovirol 16:342–354
Messaoudi I, Barron A, Wellish M, Engelmann F, Legasse A, Planer S, Gilden D, Nikolich-Zugich J, Mahalingam R (2009) Simian varicella virus infection of rhesus macaques recapitulates essential features of varicella zoster virus infection in humans. PLoS Pathog 5:e1000657
Meyer C, Kerns A, Haberthur K, Dewane J, Walker J, Gray W, Messaoudi I (2013) Attenuation of the adaptive immune response in rhesus macaques infected with simian varicella virus lacking open reading frame 61. J Virol 87:2151–2163
Ouwendijk WJ, Abendroth A, Traina-Dorge V, Getu S, Steain M, Wellish M, Andeweg AC, Osterhaus AD, Gilden D, Verjans GM, Mahalingam R (2013) T-cell infiltration correlates with CXCL10 expression in ganglia of cynomolgus macaques with reactivated simian varicella virus. J Virol 87:2979–2982
Rabalais GP, Berkowitz FE, Hayward AR, Levin MJ (1989) Inhibition of varicella-zoster virus in vitro by human peripheral blood mononuclear cells. Clin Exp Immunol 75:381–386
Selenica ML, Alvarez JA, Nash KR, Lee DC, Cao C, Lin X, Reid P, Mouton PR, Morgan D, Gordon MN (2013) Diverse activation of microglia by chemokine (C–C motif) ligand 2 overexpression in brain. J Neuroinflammation 10:86
Zak-Prelich M, McKenzie RC, Sysa-Jedrzejowska A, Norval M (2003) Local immune responses and systemic cytokine responses in zoster: relationship to the development of postherpetic neuralgia. Clin Exp Immunol 131:318–323
Zerboni L, Sen N, Oliver SL, Arvin AM (2014) Molecular mechanisms of varicella zoster virus pathogenesis. Nat Rev Microbiol 12:197–210
Acknowledgments
This work was supported in part by Public Health Service grants AG032958 (R.M, D.G., V.T-D., L.D-M., E.D., M.W., R.S.) and NS0007321 (S.J.) from the National Institutes of Health and federal funds from the National Center for Research Resources and the Office of Research Infrastructure Programs (ORIP) through grant P51 RR001464 (V.T-D., L.D-M., E.D., R.S.) at the Tulane National Primate Research Center (TNPRC).We thank members of the Pathogen Detection and Quantification Core Laboratory at TNPRC for technical assistance and Ms. Marina Hoffman for editorial assistance.
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The authors declare that they do not have any conflict of interest.
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Traina-Dorge, V., Sanford, R., James, S. et al. Robust pro-inflammatory and lesser anti-inflammatory immune responses during primary simian varicella virus infection and reactivation in rhesus macaques. J. Neurovirol. 20, 526–530 (2014). https://doi.org/10.1007/s13365-014-0274-2
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DOI: https://doi.org/10.1007/s13365-014-0274-2