Metabolism of ganciclovir and cidofovir in cells infected with drug-resistant and wild-type strains of murine cytomegalovirus

Okleberry, Kevin M.; Warren, Reed P.; Smee, Donald F.

doi:10.1016/s0166-3542(97)00013-2

Cited by 10 publications

(5 citation statements)

References 15 publications

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“…In the first set of experiments, cidofovir was shown to be phosphorylated to cidofovir-PP in uninfected, cowpox-WT-infected, and cowpox-R (SF)-infected cells to approximately the same degrees. This result was similar to its metabolism in cells infected with WT and CDV-R forms of murine cytomegalovirus (21). The degrees of phosphorylation of cidofovir in cowpox virus-infected and uninfected cells were similar, which suggests that the virus does not possess a cidofovir-phosphorylating enzyme.…”

Section: Fig 2 Treatment Of Intranasal Infections Withsupporting

confidence: 58%

“…The samples were neutralized with 10 N NaOH containing 1 M imidazole. The samples were stored at Ϫ70°C until they were analyzed with a strong anion-exchange (SAX) column (Whatman, Clifton, N.J.) by a high-pressure liquid chromatography method described previously (21). The amounts of cidofovir-PP present were expressed as picomoles of compound per 10 6 cells.…”

mentioning

confidence: 99%

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Characterization of Wild-Type and Cidofovir-Resistant Strains of Camelpox, Cowpox, Monkeypox, and Vaccinia Viruses

Smee

Sidwell

Kefauver

et al. 2002

Antimicrob Agents Chemother

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100

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Section: Fig 2 Treatment Of Intranasal Infections Withsupporting

confidence: 58%

mentioning

confidence: 99%

Characterization of Wild-Type and Cidofovir-Resistant Strains of Camelpox, Cowpox, Monkeypox, and Vaccinia Viruses

Smee

Sidwell

Kefauver

et al. 2002

Antimicrob Agents Chemother

Self Cite

124

100

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“…The 50% inhibitory concentrations for CDV were 0.17 and 0.23 M, respectively, against K181 and G4 viruses. These values are similar to previously reported values for GCV and CDV (24) and confirm that these antiviral drugs are effective against our laboratory strain and the wild isolate of MCMV.…”

Section: Resultssupporting

confidence: 92%

Ganciclovir and Cidofovir Treatment of Cytomegalovirus-Induced Myocarditis in Mice

Lenzo

Shellam

Lawson

2001

Antimicrob Agents Chemother

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The cardiovascular disease myocarditis is characterized by inflammation and necrosis of cardiac muscle. This disease has been associated with various viral etiologies, including cytomegalovirus (CMV). Murine CMV (MCMV) infection of adult BALB/c mice produces a disease with acute and chronic phases similar to that found in humans. In our murine model, we have investigated the therapeutic efficacy of antiviral drug administration on myocarditis. Two drugs commonly used for CMV treatment, ganciclovir and cidofovir, were subjected to trials, with both drugs showing potent antiviral activity against MCMV both in vitro and in vivo. The acute phase of myocarditis was significantly reduced when antiviral therapy commenced 24 h postinfection. Such treatment also reduced the severity of the chronic phase of myocarditis. In contrast, antiviral treatment commencing after the acute phase had no effect on chronic myocarditis. Reinfection of mice with MCMV caused exacerbation of myocardial inflammation. Such an increase in severity of myocarditis could be prevented with either ganciclovir or cidofovir treatment, but the preexisting inflammation and necrosis of the myocardium persisted. These data highlight possible therapeutic uses of antiviral drugs in viral myocarditis as well as further elucidating the pathogenic nature of the disease.

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“…Viral DNA synthesis and late gene expression were not required, since viral inhibition of TNF-␣-induced ICAM-1 surface expression was not sensitive to phosphonoacetic acid at 400 g/ml or cidofovir treatment at 2 g/ml at the time of infection and at the time of stimulation (Fig. 1b and data not shown) (27,37).…”

mentioning

confidence: 88%

Murine Cytomegalovirus Infection Inhibits Tumor Necrosis Factor Alpha Responses in Primary Macrophages

Popkin

Virgin

2003

J Virol

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Despite robust host immune responses the betaherpesvirus murine cytomegalovirus (MCMV) is able to establish lifelong infection. This capacity is due at least in part to the virus utilizing multiple immune evasion mechanisms to blunt host responses. Macrophages are an important cell for MCMV infection, dissemination, and latency despite expression in the host of multiple cytokines, including tumor necrosis factor alpha (TNF-␣), that can induce an antiviral state in macrophages or other cells. In this study, we found that MCMV infection of bone marrow-derived macrophages inhibited TNF-␣-induced ICAM-1 surface expression and mRNA expression in infected cells via expression of immediate early and/or early viral genes. MCMV infection blocked TNF-␣-induced nuclear translocation of NF-B. This inhibition of TNF-␣ signaling was explained by a decrease in TNF receptor 1 (TNFR1) and TNFR2 that was due to decreased mRNA for the latter. These findings provide a mechanism by which MCMV can evade the effects of an important host cytokine in macrophages.

show abstract

Metabolism of ganciclovir and cidofovir in cells infected with drug-resistant and wild-type strains of murine cytomegalovirus

Cited by 10 publications

References 15 publications

Characterization of Wild-Type and Cidofovir-Resistant Strains of Camelpox, Cowpox, Monkeypox, and Vaccinia Viruses

Characterization of Wild-Type and Cidofovir-Resistant Strains of Camelpox, Cowpox, Monkeypox, and Vaccinia Viruses

Ganciclovir and Cidofovir Treatment of Cytomegalovirus-Induced Myocarditis in Mice

Murine Cytomegalovirus Infection Inhibits Tumor Necrosis Factor Alpha Responses in Primary Macrophages

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