Gamma interferon plays a crucial early antiviral role in protection against West Nile virus infection

被引:147
作者
Shrestha, Bimmi
Wang, Tian
Samuel, Melanie A.
Whitby, Kevin
Craft, Joe
Fikrig, Erol
Diamond, Michael S.
机构
[1] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[4] Yale Univ, Sch Med, Rheumatol Sect, New Haven, CT 06520 USA
[5] Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA
关键词
D O I
10.1128/JVI.00274-06
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
West Nile virus (WNV) causes a severe central nervous system (CNS) infection in humans, primarily in the elderly and immunocompromised. Prior studies have established an essential protective role of several innate immune response elements, including alpha/beta interferon (IFN-alpha/beta), immunoglobulin M, gamma delta T cells, and complement against WNV infection. In this study, we demonstrate that a lack of IFN-gamma production or signaling results in increased vulnerability to lethal WNV infection by a subcutaneous route in mice, with a rise in mortality from 30% (wild-type mice) to 90% (IFN-gamma(-/-) or IFN-gamma R-/- mice) and a decrease in the average survival time. This survival pattern in IFN-gamma(-/-) and IFN-gamma R-/- mice correlated with higher viremia and greater viral replication in lymphoid tissues. The increase in peripheral infection led to early CNS seeding since infectious WNV was detected several days earlier in the brains and spinal cords of IFN-gamma(-/-) or IFN-gamma R-/- mice. Bone marrow reconstitution experiments showed that gamma delta T cells require IFN-gamma to limit dissemination by WNV. Moreover, treatment of primary dendritic cells with IFN-gamma reduced WNV production by 130-fold. Collectively, our experiments suggest that the dominant protective role of IFN-gamma against WNV is antiviral in nature, occurs in peripheral lymphoid tissues, and prevents viral dissemination to the CNS.
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页码:5338 / 5348
页数:11
相关论文
共 73 条
  • [1] The West Nile Virus outbreak of 1999 in New York: The flushing hospital experience
    Asnis, DS
    Conetta, R
    Teixeira, AA
    Waldman, G
    Sampson, BA
    [J]. CLINICAL INFECTIOUS DISEASES, 2000, 30 (03) : 413 - 418
  • [2] Critical role for the oligoadenylate synthetase/RNase L pathway in response to IFN-β during acute ocular herpes simplex virus type 1 infection
    Austin, BA
    James, C
    Silverman, RH
    Carr, DJJ
    [J]. JOURNAL OF IMMUNOLOGY, 2005, 175 (02) : 1100 - 1106
  • [3] Mouse neuroinvasive phenotype of West Nile virus strains varies depending upon virus genotype
    Beasley, DWC
    Li, L
    Suderman, MT
    Barrett, ADT
    [J]. VIROLOGY, 2002, 296 (01) : 17 - 23
  • [4] Prophylactic and therapeutic efficacy of human intravenous immunoglobulin in treating West Nile virus infection in mice
    Ben-Nathan, D
    Lustig, S
    Tam, G
    Robinzon, S
    Segal, S
    Rager-Zisman, B
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2003, 188 (01) : 5 - 12
  • [5] Perforin and gamma interferon-mediated control of coronavirus central nervous system infection by CD8 T cells in the absence of CD4 T cells
    Bergmann, CC
    Parra, B
    Hinton, DR
    Ramakrishna, C
    Dowdell, KC
    Stohlman, SA
    [J]. JOURNAL OF VIROLOGY, 2004, 78 (04) : 1739 - 1750
  • [6] Perforin-mediated effector function within the central nervous system requires IFN-γ-mediated MHC up-regulation
    Bergmann, CC
    Parra, B
    Hinton, DR
    Chandran, R
    Morrison, M
    Stohlman, SA
    [J]. JOURNAL OF IMMUNOLOGY, 2003, 170 (06) : 3204 - 3213
  • [7] Immune-mediated clearance of virus from the central nervous system
    Binder, GK
    Griffin, DE
    [J]. MICROBES AND INFECTION, 2003, 5 (05) : 439 - 448
  • [8] Interferon-γ-mediated site-specific clearance of alphavirus from CNS neurons
    Binder, GK
    Griffin, DE
    [J]. SCIENCE, 2001, 293 (5528) : 303 - 306
  • [9] Gamma interferon-dependent, noncytolytic clearance of Sindbis virus infection from neurons in vitro
    Burdeinick-Kerr, R
    Griffin, DE
    [J]. JOURNAL OF VIROLOGY, 2005, 79 (09) : 5374 - 5385
  • [10] BURKOW IC, 2001, NORWEGIAN POLAR I IN, V4, P1