Vaccinia virus infection attenuates innate immune responses and antigen presentation by epidermal dendritic cells Journal Article

Authors: Deng, L.; Dai, P.; Ding, W.; Granstein, R. D.; Shuman, S.
Article Title: Vaccinia virus infection attenuates innate immune responses and antigen presentation by epidermal dendritic cells
Abstract: Langerhans cells (LCs) are antigen-presenting cells in the skin that play sentinel roles in host immune defense by secreting proinflammatory molecules and activating T cells. Here we studied the interaction of vaccinia virus with XS52 cells, a murine epidermis-derived dendritic cell line that serves as a surrogate model for LCs. We found that vaccinia virus productively infects XS52 cells, yet this infection displays an atypical response to anti-poxvirus agents. Whereas adenosine N1-oxide blocked virus production and viral protein synthesis during a synchronous infection, cytosine arabinoside had no effect at concentrations sufficient to prevent virus replication in BSC40 monkey kidney cells. Vaccinia virus infection of XS52 cells not only failed to elicit the production of various cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, IL-12 p40, alpha interferon (IFN-α), and IFN-γ, it actively inhibited the production of proinflammatory cytokines TNF-α and IL-6 by XS52 cells in response to exogenous lipopolysaccharide (LPS) or poly(I:C). Infection with a vaccinia virus mutant lacking the E3L gene resulted in TNF-α secretion in the absence of applied stimuli. Infection of XS52 cells or BSC40 cells with the ΔE3L virus, but not wild-type vaccinia virus, triggered proteolytic decay of IκBα. These results suggest a novel role for the E3L protein as an antagonist of the NF-κB signaling pathway. ΔE3L-infected XS52 cells secreted higher levels of TNF-α and IL-6 in response to LPS and poly(I:C) than did cells infected with the wild-type virus. XS52 cells were productively infected by a vaccinia virus mutant lacking the K1L gene. ΔK1L-infected cells secreted higher levels of TNF-α and IL-6 in response to LPS than wild-type virus-infected cells. Vaccinia virus infection of primary LCs harvested from mouse epidermis was nonpermissive, although a viral reporter protein was expressed in the infected LCs. Vaccinia virus infection of primary LCs strongly inhibited their capacity for antigen-specific activation of T cells. Our results highlight suppression of the skin immune response as a feature of orthopoxvirus infection. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Keywords: signal transduction; controlled study; unclassified drug; gene deletion; nonhuman; alpha interferon; cytarabine; animal cell; mouse; animals; mice; dendritic cell; protein degradation; interleukin 10; interleukin 1beta; cell line; animal experiment; animal model; immunoglobulin enhancer binding protein; cercopithecus aethiops; wild type; rna-binding proteins; cytokine; antigen presentation; cytokines; tumor necrosis factor alpha; gamma interferon; protein synthesis; adenosine; murinae; vaccinia virus; interleukin 6; lipopolysaccharide; polyinosinic polycytidylic acid; cytokine production; innate immunity; virus replication; cytokine release; monkey; antigen presenting cell; t lymphocyte activation; interleukin 12; virus mutant; virus protein; viral proteins; antiviral agents; poxviridae; vaccinia; protein p40; langerhans cell; langerhans cells; virogenesis; virus gene; virus inhibition; i-kappa b proteins; immunity, natural; epidermis cell; i kappa b alpha; genes, viral; protein e3l; proteni k1l; orthopoxvirus; cyclic n-oxides
Journal Title: Journal of Virology
Volume: 80
Issue: 20
ISSN: 0022-538X
Publisher: American Society for Microbiology  
Date Published: 2006-10-01
Start Page: 9977
End Page: 9987
Language: English
DOI: 10.1128/jvi.00354-06
PUBMED: 17005676
PROVIDER: scopus
PMCID: PMC1617288
Notes: --- - "Cited By (since 1996): 27" - "Export Date: 4 June 2012" - "CODEN: JOVIA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Liang Deng
    65 Deng
  2. Stewart H Shuman
    518 Shuman
  3. Peihong Dai
    38 Dai