title: Mice deficient in interferon-gamma or interferon-gamma receptor 1 have distinct inflammatory responses to acute viral encephalomyelitis.
abstract: Interferon (IFN)-gamma is an important component of the immune response to viral infections that can have a role both in controlling virus replication and inducing inflammatory damage. To determine the role of IFN-gamma in fatal alphavirus encephalitis, we have compared the responses of wild type C57BL/6 (WTB6) mice with mice deficient in either IFN-gamma (GKO) or the alpha-chain of the IFN-gamma receptor (GRKO) after intranasal infection with a neuroadapted strain of sindbis virus. Mortalities of GKO and GRKO mice were similar to WTB6 mice. Both GKO and GRKO mice had delayed virus clearance from the brain and spinal cord, more infiltrating perforin(+) cells and lower levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mRNAs than WTB6 mice. However, inflammation was more intense in GRKO mice than WTB6 or GKO mice with more infiltrating CD3(+) T cells, greater expression of major histocompatibility complex-II and higher levels of interleukin-17A mRNA. Fibroblasts from GRKO embryos did not develop an antiviral response after treatment with IFN-gamma, but showed increases in TNF-alpha, IL-6, CXCL9 and CXCL10 mRNAs although these increases developed more slowly and were less intense than those of WTB6 fibroblasts. These data indicate that both GKO and GRKO mice fail to develop an IFN-gamma-mediated antiviral response, but differ in regulation of the inflammatory response to infection. Therefore, GKO and GRKO cannot be considered equivalent when assessing the role of IFN-gamma in CNS viral infections.
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Lee
authors.forename: Kimberly L W
authors.initials: KL
authors.lastname: Schultz
authors.forename: Diane E
authors.initials: DE
authors.lastname: Griffin
mesh_terms: D018354:Alphavirus Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004679:Encephalomyelitis / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000821:virology*; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012845:Sindbis Virus / Q000502:physiology; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication; D000096743:Interferon gamma Receptor
chemical_list: D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D017471:Receptors, Interferon; D017361:Viral Nonstructural Proteins; D000096743:Interferon gamma Receptor