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


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

  • 21334039

Electronic International Standard Serial Number (EISSN)

  • 1096-0341

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2011.01.024


  • eng

Conference Location

  • United States