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Titolo:
TRANSGENIC EXPRESSION OF IFN-ALPHA IN THE CENTRAL-NERVOUS-SYSTEM OF MICE PROTECTS AGAINST LETHAL NEUROTROPIC VIRAL-INFECTION BUT INDUCES INFLAMMATION AND NEURODEGENERATION
Autore:
AKWA Y; HASSETT DE; ELORANTA ML; SANDBERG K; MASLIAH E; POWELL H; WHITTON JL; BLOOM FE; CAMPBELL IL;
Indirizzi:
SCRIPPS CLIN & RES INST,DEPT NEUROPHARMACOL,CVN-9,10550 N TORREY PINES RD LA JOLLA CA 92037 SCRIPPS CLIN & RES INST,DEPT NEUROPHARMACOL LA JOLLA CA 92037 SWEDISH UNIV AGR SCI,DEPT VET MICROBIOL,DIV IMMUNOL UPPSALA SWEDEN ASTRA ARCUS AB SODERTALJE SWEDEN UNIV SAN DIEGO,DEPT PATHOL SAN DIEGO CA 92110
Titolo Testata:
The Journal of immunology (1950)
fascicolo: 9, volume: 161, anno: 1998,
pagine: 5016 - 5026
SICI:
0022-1767(1998)161:9<5016:TEOIIT>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
LYMPHOCYTIC CHORIOMENINGITIS VIRUS; PROGRESSIVE FAMILIAL ENCEPHALOPATHY; CEREBROSPINAL-FLUID LYMPHOCYTOSIS; INTERFERON-ALPHA; TUBULORETICULAR STRUCTURES; PRIMARY DEMYELINATION; IMMUNE-RESPONSE; HERPES-SIMPLEX; BASAL GANGLIA; DISEASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
54
Recensione:
Indirizzi per estratti:
Citazione:
Y. Akwa et al., "TRANSGENIC EXPRESSION OF IFN-ALPHA IN THE CENTRAL-NERVOUS-SYSTEM OF MICE PROTECTS AGAINST LETHAL NEUROTROPIC VIRAL-INFECTION BUT INDUCES INFLAMMATION AND NEURODEGENERATION", The Journal of immunology (1950), 161(9), 1998, pp. 5016-5026

Abstract

Type I IFNs, which include IFN-alpha, appear to have complex and broad-ranging actions in the central nervous system (CNS) that may result in protection or injury. To better understand these issues, we generated transgenic mice that produce IFN-alpha, chronically from astrocytes, These glial fibrillary acidic protein-IFN-alpha transgenic mice developed a progressive inflammatory encephalopathy, with marked calcium mineralization, meninoencephalitis, gliosis, and neurodegeneration. Many features of this murine encephalopathy resembled those found in certain human encephalopathies of unknown etiology; these diseases, exemplified by Aicardi-Goutieres syndrome and some viral encephalopathies, show increased intrathecal production of IFN-alpha, Our data suggest that IFN-alpha overproduction may be the primary factor initiating thesehuman diseases. Following intracerebral infection with Iymphocytic choriomeningitis virus, glial fibrillary acidic protein-IFN-alpha mice had significantly increased survival rates associated with markedly reduced virus titers and immune pathology in the brain but normal peripheral CTL responses. Therefore, the production of IFN-alpha in the CNS can be a two-edged sword that on the one hand confers protection against a lethal viral infection but on the other causes significant injury to the brain. These transgenic mice provide a novel animal model in which to further evaluate the mechanisms that underlie the diverse actions of type I IFNs in the intact CNS.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 17:57:02