Cowpox virus inhibits human dendritic cell immune function by nonlethal, nonproductive infection.
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-κB 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.
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Related Subject Headings
- Virology
- NF-kappa B
- Immune Evasion
- Humans
- Dendritic Cells
- Cytokines
- Cowpox virus
- Cells, Cultured
- Cell Survival
- 32 Biomedical and clinical sciences
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Virology
- NF-kappa B
- Immune Evasion
- Humans
- Dendritic Cells
- Cytokines
- Cowpox virus
- Cells, Cultured
- Cell Survival
- 32 Biomedical and clinical sciences