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Titolo:
Immunological effects of the orally administered neuraminidase inhibitor oseltamivir in influenza virus-infected and uninfected mice
Autore:
Burger, RA; Billingsley, JL; Huffman, JH; Bailey, KW; Kim, CU; Sidwell, RW;
Indirizzi:
Utah State Univ, Ctr Persons Disabil, Logan, UT 84322 USA Utah State UnivLogan UT USA 84322 r Persons Disabil, Logan, UT 84322 USA Utah State Univ, Dept Anim Dairy & Vet Sci, Inst Antiviral Res, Logan, UT 84322 USA Utah State Univ Logan UT USA 84322 nst Antiviral Res, Logan, UT 84322 USA Gilead Sci Inc, Foster City, CA 94404 USA Gilead Sci Inc Foster City CA USA 94404 ci Inc, Foster City, CA 94404 USA
Titolo Testata:
IMMUNOPHARMACOLOGY
fascicolo: 1, volume: 47, anno: 2000,
pagine: 45 - 52
SICI:
0162-3109(200004)47:1<45:IEOTOA>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
4-GUANIDINO-2,4-DIDEOXY-2,3-DEHYDRO-N-ACETYLNEURAMINIC ACID; A VIRUS; REPLICATION; SIALIDASE; PRODRUG; GS-4071; GS4104; DESIGN; GG167;
Keywords:
influenza; oseltamivir; GS4104; natural killer cell; cytotoxic T cell; neuraminidase inhibitor; macrophage; antiviral;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Burger, RA Utah State Univ, Ctr Persons Disabil, Logan, UT 84322 USA Utah State Univ Logan UT USA 84322 isabil, Logan, UT 84322 USA
Citazione:
R.A. Burger et al., "Immunological effects of the orally administered neuraminidase inhibitor oseltamivir in influenza virus-infected and uninfected mice", IMMUNOPHARM, 47(1), 2000, pp. 45-52

Abstract

Oseltamivir (GS4104), the ethyl ester prodrug of the carbocyclic transition state sialic acid analog GS4071, has been reported to be a striking inhibitor of influenza A and B virus infections in mice and ferrets. Multiple studies indicate this material to also be active against the disease in humans, and it has recently been approved for human use. The effect of oral gavage (p.o.) therapy of oseltamivir on various immune factors considered to beof importance in primary influenza virus infection was studied in mice. Both uninfected animals and those infected with influenza A/NWS/33 (H1N1) virus were used. Doses of 100 mg kg(-1) day(-1) were administered twice daily for 5 days beginning 16 h pre-virus exposure. Two hours after end of treatment, the mice were killed and their spleens assayed for cytotoxic T lymphocyte (CTL) and natural killer (NK) cell activity. Subpopulations of splenic T, T-helper, T-cytotoxic and B lymphocytes as well as macrophages were determined using flow cytometry. Similar significant (P < 0.01) increases in CTL activity were seen at effector:target cell ratios of 60:1 and 30:1 in theinfected mice treated with oseltamivir or with placebo. NK cell activity was greater in the infected mice than in uninfected mice; the levels in all animals were not significantly affected by treatment with oseltamivir. Macrophage, T, T-helper, T-cytotoxic and B lymphocyte populations were similar in both treated and untreated animals. These data indicate treatment with oseltamivir does not adversely affect the primary in vivo cellular immune responses to influenza virus infection assayed in this study. The experiment was repeated to show that treatment with this compound significantly prevented the development of the infection and inhibited virus titers in the lung. Surviving treated mice on day 21 had mean neutralizing antibody titers of1:208, and withstood rechallenge with the virus at this time, indicating the initial virus-inhibitory effect also did not prevent the animals from developing an adequate humoral immunity to the virus. (C) 2000 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 18:01:13