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Titolo:
ANTIVIRAL ACTIVITIES OF NUCLEOSIDES AND NUCLEOTIDES AGAINST WILD-TYPEAND DRUG-RESISTANT STRAINS OF MURINE CYTOMEGALOVIRUS
Autore:
SMEE DF; BARNETT BB; SIDWELL RW; REIST EJ; HOLY A;
Indirizzi:
UTAH STATE UNIV,DEPT ANIM DAIRY & VET SCI,INST ANTIVIRAL RES LOGAN UT84322 UTAH STATE UNIV,DEPT BIOL LOGAN UT 84322 SRI INT MENLO PK CA 94025 ACAD SCI CZECH REPUBL,INST ORGAN CHEM & BIOCHEM PRAGUE CZECH REPUBLIC
Titolo Testata:
Antiviral research
fascicolo: 1, volume: 26, anno: 1995,
pagine: 1 - 9
SICI:
0166-3542(1995)26:1<1:AAONAN>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA-POLYMERASE GENE; PHOSPHONYLMETHOXYALKYL DERIVATIVES; GANCICLOVIR; VIRUS; INFECTIONS; FOSCARNET; AGENTS; RETINITIS; PROTEIN;
Keywords:
MURINE CYTOMEGALOVIRUS; GANCICLOVIR; FOSCARNET; HPMPC; ANTIVIRAL; DRUG RESISTANCE; NUCLEOSIDE; NUCLEOTIDE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
25
Recensione:
Indirizzi per estratti:
Citazione:
D.F. Smee et al., "ANTIVIRAL ACTIVITIES OF NUCLEOSIDES AND NUCLEOTIDES AGAINST WILD-TYPEAND DRUG-RESISTANT STRAINS OF MURINE CYTOMEGALOVIRUS", Antiviral research, 26(1), 1995, pp. 1-9

Abstract

Resistance of human cytomegalovirus to approved antiviral drugs is becoming a problem of increasing concern. In order to further study drugresistance in a related virus, strains of murine cytomegalovirus (MCMV) have been prepared in vitro by extensive adaptation of the virus toincreasingly higher concentrations of either ganciclovir, foscarnet, or -9-(3-hydroxy-2-[phosphonylmethoxy]propyl)cytosine (HPMPC). Plaque reduction 50% effective concentrations (EC(50)) for the above inhibitors increased 9-, 7-, and 23-fold, respectively (against the corresponding virus), compared to wild-type MCMV. Each virus was then evaluated against other known anti-MCMV agents to determine cross-resistance patterns. These compounds included 3-hydroxy-phosphonylmethoxypropyl derivatives of adenine (HPMPA) and guanine (HPMPG), 2-phosphonylmethoxyethyl derivatives of adenine (PMEA) and 2,6-diaminopurine (PMEDAP), cyclobutylguanine, acyclovir, and the methylene phosphonate derivatives of acyclovir (SR3722) and ganciclovir (SR3773). The ganciclovir-resistantMCMV was cross-resistant to foscarnet, HPMPA, HPMPC, HPMPG, SR3722, and SR3773. The foscarnet-resistant virus was also resistant to acyclovir, PMEA, PMEDAP, SR3722, and SR3773. The HPMPC-resistant MCMV was cross-resistant to HPMPA, HPMPG, and SR3773. Changes in susceptibility were from 3- to 22-fold relative to the wild-type virus. Virus yield reduction data correlated with the plaque assay results. Only cyclobutylguanine was approximately equally active against wild-type and the three drug-resistant MCMVs. The patterns of cross-resistance correlated with resistance seen in human cytomegalovirus strains expressing alteredDNA polymerase function. The GCV-resistant and HPMPC-resistant viruses were markedly attenuated in their ability to kill severe combined immunodeficient mice.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/08/20 alle ore 08:29:37