Murine gamma-herpesvirus-68-induced IL-12 contributes to the control of latent viral burden, but also contributes to viral-mediated leukocytosis.

Academic Article


  • Early IFN-alpha/beta production, followed by the development of a viral-specific CTL response, are critical factors in limiting the level of murine gamma-herpesvirus-68 (gammaHV-68) infection. Development of a long-lived CTL response requires T cell help, and these CTLs most likely function to limit the extent of infection following reactivation. The importance of IL-12 in the development and/or activity of Th1 cells and CTLs is well documented, and we investigated the kinetics and magnitude of gammaHV-68-induced IL-12 production. Following intranasal infection, IL-12 and IL-23 mRNA expression was up-regulated in lung and spleen and lung, respectively, followed by increased levels of IL-12p40 in lung homogenates and sera. Exposure of cultured macrophages or dendritic cells to gammaHV-68 induced secretion of IL-12, suggesting that these cells might be responsible for IL-12 production in vivo. gammaHV-68 infection of mice made genetically deficient in IL-12p40 expression (IL-12p40(-/-)) resulted in a leukocytosis and splenomegaly that was significantly less than that observed in syngeneic C57BL/6 mice. IL-12p40(-/-) mice showed increased levels of infectious virus in the lung, but only at day 9 postinfection. Increased levels of latent virus in the spleen at day 15 postinfection were also observed in IL-12p40(-/-) mice when compared with syngeneic C57BL/6 mice. An overall reduction in gammaHV-68-induced IFN-gamma production was observed in IL-12p40(-/-) mice, suggesting that most of the viral-induced IFN-gamma in C57BL/6 mice was IL-12 dependent. Taken together, these results suggest that gammaHV-68-induced IL-12 contributes to the pathophysiology of viral infection while also functioning to limit viral burden.
  • Authors

  • Elsawa, Sherine
  • Bost, Kenneth L
  • Status

    Publication Date

  • January 1, 2004
  • Published In


  • Acute Disease
  • Animals
  • Bone Marrow Cells
  • Cells, Cultured
  • Dendritic Cells
  • Herpesviridae Infections
  • Humans
  • Interferon-gamma
  • Interleukin-12
  • Interleukin-12 Subunit p40
  • Leukocytosis
  • Macrophages, Peritoneal
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Protein Subunits
  • Rhadinovirus
  • Splenomegaly
  • Tumor Virus Infections
  • Viral Load
  • Virus Latency
  • Digital Object Identifier (doi)

    Pubmed Id

  • 14688362
  • Start Page

  • 516
  • End Page

  • 524
  • Volume

  • 172
  • Issue

  • 1