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Titolo:
AN IMMUNOSUPPRESSED MOUSE MODEL OF LETHAL MURINE GAMMAHERPESVIRUS-68 INFECTION FOR STUDYING POTENTIAL TREATMENT OF EPSTEIN-BARR-VIRUS INFECTION IN MAN
Autore:
SMEE DF; BURGER RA; WARREN RP; BAILEY KW; SIDWELL RW;
Indirizzi:
UTAH STATE UNIV,DEPT ANIM DAIRY & VET SCI,INST ANTIVIRAL RES LOGAN UT84322 UTAH STATE UNIV,DEPT ANIM DAIRY & VET SCI,INST ANTIVIRAL RES LOGAN UT84322
Titolo Testata:
Antiviral chemistry & chemotherapy
fascicolo: 6, volume: 8, anno: 1997,
pagine: 573 - 581
SICI:
0956-3202(1997)8:6<573:AIMMOL>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
LYMPHOPROLIFERATIVE DISORDERS; CYTOMEGALOVIRUS; MICE; ACYCLOVIR; CELLS; REPLICATION; GANCICLOVIR; IMMUNODEFICIENCY; ANALOGS; -1-)3-HYDROXY-2-(PHOSPHONYLMETHOXY)PROPYL>CYTOSINE;
Keywords:
EPSTEIN-BARR VIRUS; GAMMAHERPESVIRUS; IMMUNOSUPPRESSION; ANTIVIRAL; ACYCLOVIR; CIDOFOVIR;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
43
Recensione:
Indirizzi per estratti:
Citazione:
D.F. Smee et al., "AN IMMUNOSUPPRESSED MOUSE MODEL OF LETHAL MURINE GAMMAHERPESVIRUS-68 INFECTION FOR STUDYING POTENTIAL TREATMENT OF EPSTEIN-BARR-VIRUS INFECTION IN MAN", Antiviral chemistry & chemotherapy, 8(6), 1997, pp. 573-581

Abstract

Murine gammaherpesvirus 68 (MHV-68) is a rodent virus related to human Epstein-Barr virus (EBV). MHV-68 infection and its treatment were studied in a novel lethal immunosuppression model in BALB/c mice. Intranasally infected mice that were immunosuppressed with cyclophosphamide developed persistently high virus titres in pulmonary tissue, and to alesser extent, in splenic tissue. These animals died from infection within 12 days, whereas normal mice resolved the infection by day 10 and survived. Cyclophosphamide-treated infected mice had significant decreases in natural killer cell activity, T and B cell proliferative responses, and T and B cell numbers compared to immunocompetent uninfected and infected animals. In order to study the treatment of the lethal infection, 16 known inhibitors of EBV or other herpesviruses were first evaluated against MHV-68 by plaque reduction assay in African green monkey kidney (MA-104) cells. Of these compounds, fialuridine (FIAU) had the most potent effect, inhibiting 50% of viral plaques at 0.1 mu M. By comparison, cidofovir (HPMPC), HPMPA, acyclovir and ganciclovir were inhibitory at 1.2, 0.9, 6.7 and 10 mu M respectively. Cyclophosphamide-immunosuppressed infected mice were treated intraperitoneally with acyclovir, FIAU, HPMPC or placebo for 5 days starting 24 h after virus challenge. Acyclovir treatment (70 mg kg(-1) day(-1)) did not increase survival time significantly but decreased lung virus titres sixfold as measured on day 9 of the infection; FIAU treatments (5 mg kg(-1) day(-1)) caused a 2.4 day delay in death and reduced lung virus titresgreater than 15-fold. HPMPC treatments (5 mg kg(-1) day(-1)) resultedin a 13 day delay in death, and reduced virus production in the lung over 3000-fold compared with the placebo group. HPMPC appears to be anexcellent candidate for treating EBV virus infections in humans, particularly in immunocompromised patients in whom infections may be life-threatening.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/07/20 alle ore 05:16:34