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Cowpox virus inhibits human dendritic cell immune function by nonlethal, nonproductive infection.


ABSTRACT: Orthopoxviruses encode multiple proteins that modulate host immune responses. We determined whether cowpox virus (CPXV), a representative orthopoxvirus, modulated innate and acquired immune functions of human primary myeloid DCs and plasmacytoid DCs and monocyte-derived DCs (MDDCs). A CPXV infection of DCs at a multiplicity of infection of 10 was nonproductive, altered cellular morphology, and failed to reduce cell viability. A CPXV infection of DCs did not stimulate cytokine or chemokine secretion directly, but suppressed toll-like receptor (TLR) agonist-induced cytokine secretion and a DC-stimulated mixed leukocyte reaction (MLR). LPS-stimulated NF-?B nuclear translocation and host cytokine gene transcription were suppressed in CPXV-infected MDDCs. Early viral immunomodulatory genes were upregulated in MDDCs, consistent with early DC immunosuppression via synthesis of intracellular viral proteins. We conclude that a nonproductive CPXV infection suppressed DC immune function by synthesizing early intracellular viral proteins that suppressed DC signaling pathways.

SUBMITTER: Hansen SJ 

PROVIDER: S-EPMC3694803 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Cowpox virus inhibits human dendritic cell immune function by nonlethal, nonproductive infection.

Hansen Spencer J SJ   Rushton John J   Dekonenko Alexander A   Chand Hitendra S HS   Olson Gwyneth K GK   Hutt Julie A JA   Pickup David D   Lyons C Rick CR   Lipscomb Mary F MF  

Virology 20110221 2


Orthopoxviruses encode multiple proteins that modulate host immune responses. We determined whether cowpox virus (CPXV), a representative orthopoxvirus, modulated innate and acquired immune functions of human primary myeloid DCs and plasmacytoid DCs and monocyte-derived DCs (MDDCs). A CPXV infection of DCs at a multiplicity of infection of 10 was nonproductive, altered cellular morphology, and failed to reduce cell viability. A CPXV infection of DCs did not stimulate cytokine or chemokine secret  ...[more]

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