title: Murine gamma-herpesvirus-68-induced IL-12 contributes to the control of latent viral burden, but also contributes to viral-mediated leukocytosis.
abstract: 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.affiliation: Department of Biology, University of North Carolina, 9201 University City Boulevard, Charlotte, NC 28223, USA.
authors.forename: Sherine F
authors.initials: SF
authors.lastname: Elsawa
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Bost
mesh_terms: D000208:Acute Disease; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053762:Interleukin-12 Subunit p40; D007964:Leukocytosis / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics; D018144:Rhadinovirus / Q000276:immunology*; D013163:Splenomegaly / Q000235:genetics / Q000276:immunology / Q000821:virology; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D019562:Viral Load; D017735:Virus Latency / Q000276:immunology*
chemical_list: D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D018664:Interleukin-12; D007371:Interferon-gamma