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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Hansen, SJ; Rushton, J; Dekonenko, A; Chand, HS; Olson, GK; Hutt, JA; Pickup, D; Lyons, CR; Lipscomb, MF

Published Date

  • April 10, 2011

Published In

Volume / Issue

  • 412 / 2

Start / End Page

  • 411 - 425

PubMed ID

  • 21334039

Pubmed Central ID

  • PMC3694803

Electronic International Standard Serial Number (EISSN)

  • 1096-0341

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2011.01.024

Language

  • eng

Conference Location

  • United States