Selective suppression of IL-12 production by human herpesvirus 6

Alison Smith, Fabio Santoro, Giulia Di Lullo, Lorenzo Dagna, Alessla Verani, Paolo Lusso

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Abstract

Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that has been suggested to act as a cofactor in the progression of HIV disease. Exposure of human macrophages to HHV-6A or HHV-6B profoundly impaired their ability to produce interleukin 12 (IL-12) upon stimulation with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). By contrast, the production of tumor necrosis factor-α (TNF-α); regulated on activation, normal T-cell expressed and secreted (RANTES); and macrophage inflammatory protein 1β (MIP-1β) was not negatively affected. To exclude the involvement of IL-12-suppressive cytokines, such as IL-10 and TNF-α, the viral stocks were fractionated by ultracentrifugation. The bulk of the suppressive activity was recovered within the virion-rich pelleted fraction that was virtually devoid of such cytokines. IL-12 suppression was independent of viral replication, and the effect was not abrogated upon ultraviolet-light inactivation of the viral inoculum. The mechanism of HHV-6-mediated IL-12 suppression was investigated by RNase protection assays, which demonstrated unaltered levels of IL-12 p35 mRNA and only a modest reduction in p40 mRNA, which was insufficient to account for the near-complete loss of both extracellular and intracellular IL-12 protein. Moreover, both the IFN-γ and the LPS signaling pathways were intact in HHV-6-treated cells. These data suggest that HHV-6 can dramatically affect the generation of effective cellular immune responses, providing a novel potential mechanism of HHV-6-mediated immunosuppression.

Original languageEnglish
Pages (from-to)2877-2884
Number of pages8
JournalBlood
Volume102
Issue number8
DOIs
Publication statusPublished - Oct 15 2003

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ASJC Scopus subject areas

  • Hematology

Cite this

Smith, A., Santoro, F., Di Lullo, G., Dagna, L., Verani, A., & Lusso, P. (2003). Selective suppression of IL-12 production by human herpesvirus 6. Blood, 102(8), 2877-2884. https://doi.org/10.1182/blood-2002-10-3152