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

• Published in: Virology (New York, N.Y.) N.Y.), 2011-04, Vol.412 (2), p.411-425
• Main Authors: Hansen, Spencer J, Rushton, John, Dekonenko, Alexander, Chand, Hitendra S, Olson, Gwyneth K, Hutt, Julie A, Pickup, David, Lyons, C. Rick, Lipscomb, Mary F
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ANIMAL CELLS; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; Cell Survival; Cells, Cultured; Chemokines; CONNECTIVE TISSUE CELLS; Cowpox virus; Cowpox virus - immunology; Cowpox virus - pathogenicity; Cytokines; Cytokines - antagonists & inhibitors; Cytokines - secretion; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - virology; GENES; GROWTH FACTORS; Humans; Immune Evasion; IMMUNOSUPPRESSION; Infectious Disease; LEUKOCYTES; LYMPHOCYTES; LYMPHOKINES; MATERIALS; MEMBRANE PROTEINS; MICROORGANISMS; MITOGENS; Mixed lymphocyte reaction; MONOCYTES; MORPHOLOGY; Myeloid dendritic cells; NF-kappa B - antagonists & inhibitors; NF-kappa B - immunology; ORGANIC COMPOUNDS; Orthopoxvirus; Orthopoxviruses; PARASITES; Plasmacytoid dendritic cells; PROTEINS; RECEPTORS; SECRETION; SOMATIC CELLS; TRANSCRIPTION; Viral microarray; VIRUSES
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2011.01.024

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-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.