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75 Keller, B.C., Fredericksen, B.L., Samuel, M.A., Mock, R.E., Mason, P.W., Diamond, M.S., Gale, M. Jr., Resistance to alpha/beta interferon is a determinant of West Nile virus replication fitness and virulence. J Virol 80 (2006), 9424–9434.
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76 Mansfield, K.L., Johnson, N., Cosby, S.L., Solomon, T., Fooks, A.R., Transcriptional upregulation of SOCS 1 and suppressors of cytokine signaling 3 mRNA in the absence of suppressors of cytokine signaling 2 mRNA after infection with West Nile virus or tick-borne encephalitis virus. Vector Borne Zoonotic Dis 10 (2010), 649–653.
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This study shows that several enveloped viruses including WNV bind to and activate TAM receptors on dendritic cells, thereby dampening type I IFN signaling.
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77• Bhattacharyya, S., Zagorska, A., Lew, E.D., Shrestha, B., Rothlin, C.V., Naughton, J., Diamond, M.S., Lemke, G., Young, J.A., Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors. Cell Host Microbe 14 (2013), 136–147 This study shows that several enveloped viruses including WNV bind to and activate TAM receptors on dendritic cells, thereby dampening type I IFN signaling.
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78 Mackenzie, J.M., Khromykh, A.A., Parton, R.G., Cholesterol manipulation by West Nile virus perturbs the cellular immune response. Cell Host Microbe 2 (2007), 229–239.
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79 Evans, J.D., Crown, R.A., Sohn, J.A., Seeger, C., West Nile virus infection induces depletion of IFNAR1 protein levels. Viral Immunol 24 (2011), 253–263.
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80 Liu, W.J., Wang, X.J., Mokhonov, V.V., Shi, P.Y., Randall, R., Khromykh, A.A., Inhibition of interferon signaling by the New York 99 strain and Kunjin subtype of West Nile virus involves blockage of STAT1 and STAT2 activation by nonstructural proteins. J Virol 79 (2005), 1934–1942.
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81 Ashour, J., Laurent-Rolle, M., Shi, P.Y., Garcia-Sastre, A., NS5 of dengue virus mediates STAT2 binding and degradation. J Virol 83 (2009), 5408–5418.
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82 Mazzon, M., Jones, M., Davidson, A., Chain, B., Jacobs, M., Dengue virus NS5 inhibits interferon-alpha signaling by blocking signal transducer and activator of transcription 2 phosphorylation. J Infect Dis 200 (2009), 1261–1270.
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83 Laurent-Rolle, M., Boer, E.F., Lubick, K.J., Wolfinbarger, J.B., Carmody, A.B., Rockx, B., Liu, W., Ashour, J., Shupert, W.L., Holbrook, M.R., et al. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol 84 (2010), 3503–3515.
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84 Morrison, J., Laurent-Rolle, M., Maestre, A.M., Rajsbaum, R., Pisanelli, G., Simon, V., Mulder, L.C., Fernandez-Sesma, A., Garcia-Sastre, A., Dengue virus co-opts UBR4 to degrade STAT2 and antagonize type I interferon signaling. PLoS Pathog, 9, 2013, e1003265.
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85 Ashour, J., Morrison, J., Laurent-Rolle, M., Belicha-Villanueva, A., Plumlee, C.R., Bernal-Rubio, D., Williams, K.L., Harris, E., Fernandez-Sesma, A., Schindler, C., et al. Mouse STAT2 restricts early dengue virus replication. Cell Host Microbe 8 (2010), 410–421.
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86 Suthar, M.S., Brassil, M.M., Blahnik, G., Gale, M. Jr., Infectious clones of novel lineage 1 and lineage 2 West Nile virus strains WNV-TX02 and WNV-Madagascar. J Virol 86 (2012), 7704–7709.
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A Mouse Model of Zika Virus Pathogenesis
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The authors evaluate infection and pathogenesis with contemporary and historical ZIKV strains in immunocompetent mice and mice lacking key molecules of the IFN response, and show that Ifnar1 or Irf3/5/7 knockout mice develop neurological disease and succumb to ZIKV infection.
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87•• Lazear, H.M., Govero, J., Smith, A.M., Platt, D.J., Fernandez, E., Miner, J.J., Diamond, M.S., A Mouse Model of Zika Virus Pathogenesis. Cell Host Microbe 19 (2016), 720–730 The authors evaluate infection and pathogenesis with contemporary and historical ZIKV strains in immunocompetent mice and mice lacking key molecules of the IFN response, and show that Ifnar1 or Irf3/5/7 knockout mice develop neurological disease and succumb to ZIKV infection.
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88
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This study establishes two mouse models of in utero transmission and fetal disease associated with ZIKV infection, which may facilitate future studies to test therapies and vaccines to prevent congenital malformations.
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88•• Miner, J.J., Cao, B., Govero, J., Smith, A.M., Fernandez, E., Cabrera, O.H., Garber, C., Noll, M., Klein, R.S., Noguchi, K.K., et al. Zika virus infection during pregnancy in mice causes placental damage and fetal demise. Cell 165 (2016), 1081–1091 This study establishes two mouse models of in utero transmission and fetal disease associated with ZIKV infection, which may facilitate future studies to test therapies and vaccines to prevent congenital malformations.
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89
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This paper demonstrates that the NS5 protein of ZIKV induces the proteasomal degradation of the transcriptional activator STAT2. This mechanism functions for human but not mouse STAT2, which in part, could explain species restriction of ZIKV.
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89• Grant, A., Ponia, S.S., Tripathi, S., Balasubramaniam, V., Miorin, L., Sourisseau, M., Schwarz, M.C., Sanchez-Seco, M.P., Evans, M.J., Best, S.M., et al. Zika virus targets human STAT2 to inhibit type I interferon signaling. Cell Host Microbe, 2016 This paper demonstrates that the NS5 protein of ZIKV induces the proteasomal degradation of the transcriptional activator STAT2. This mechanism functions for human but not mouse STAT2, which in part, could explain species restriction of ZIKV.
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Grant, A.1
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Analysis of adaptive mutations in Kunjin virus replicon RNA reveals a novel role for the flavivirus nonstructural protein NS2A in inhibition of beta interferon promoter-driven transcription
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90 Liu, W.J., Chen, H.B., Wang, X.J., Huang, H., Khromykh, A.A., Analysis of adaptive mutations in Kunjin virus replicon RNA reveals a novel role for the flavivirus nonstructural protein NS2A in inhibition of beta interferon promoter-driven transcription. J Virol 78 (2004), 12225–12235.
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91 Liu, W.J., Wang, X.J., Clark, D.C., Lobigs, M., Hall, R.A., Khromykh, A.A., A single amino acid substitution in the West Nile virus nonstructural protein NS2A disables its ability to inhibit alpha/beta interferon induction and attenuates virus virulence in mice. J Virol 80 (2006), 2396–2404.
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