title: 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-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.
authors.affiliation: Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA. sjhansen@email.arizona.edu
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Hansen
authors.forename: John
authors.initials: J
authors.lastname: Rushton
authors.forename: Alexander
authors.initials: A
authors.lastname: Dekonenko
authors.forename: Hitendra S
authors.initials: HS
authors.lastname: Chand
authors.forename: Gwyneth K
authors.initials: GK
authors.lastname: Olson
authors.forename: Julie A
authors.initials: JA
authors.lastname: Hutt
authors.forename: David
authors.initials: D
authors.lastname: Pickup
authors.forename: C Rick
authors.initials: CR
authors.lastname: Lyons
authors.forename: Mary F
authors.initials: MF
authors.lastname: Lipscomb
mesh_terms: D002470:Cell Survival; D002478:Cells, Cultured; D015608:Cowpox virus / Q000276:immunology* / Q000472:pathogenicity*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D006801:Humans; D057131:Immune Evasion; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D016207:Cytokines; D016328:NF-kappa B