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The dynamics of human cytomegalovirus replication in vivo.

Emery VC, Cope AV, Bowen EF, Gor D, Griffiths PD - J. Exp. Med. (1999)

Bottom Line: The results from all three approaches demonstrated that the doubling time/half-life of CMV in blood is approximately 1 d when frequent samples are collected.These results show that CMV DNA replication in vivo is a highly dynamic process.We conclude that the reputation of CMV as a slowly replicating virus based on the time taken to produce cytopathic effects in vitro is unwarranted.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Royal Free and University College Medical School of University College London, London NW3 2QG, United Kingdom. vincent@rfhsm.ac.uk

ABSTRACT
Cytomegalovirus (CMV) is generally described as a slowly replicating virus. During studies of immunocompromised patients, we observed rapid changes in the quantity of CMV DNA present in serial blood samples by quantitative-competitive polymerase chain reaction commensurate with a doubling time of <2 d. To further investigate the dynamics of replication in vivo, patients in three distinct situations were studied in detail: (a) those receiving intravenous ganciclovir; (b) those in whom ganciclovir-resistant strains appeared during long-term therapy; and (c) those in whom ganciclovir-resistant strains disappeared with alternative drug therapy. In all cases, it was possible to provide accurate estimates of the doubling time of CMV and its half-life of disappearance after antiviral chemotherapy. The results from all three approaches demonstrated that the doubling time/half-life of CMV in blood is approximately 1 d when frequent samples are collected. These results show that CMV DNA replication in vivo is a highly dynamic process. We conclude that the reputation of CMV as a slowly replicating virus based on the time taken to produce cytopathic effects in vitro is unwarranted. These findings have implications for the potency, dose, and duration of antiviral chemotherapy needed for the effective treatment of this important human pathogen.

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Reduction in CMV load in the blood of five AIDS retinitis patients subjected to intensive sampling after initiation of intravenous GCV therapy. The data points are represented as filled circles, and the computed line of best fit is shown.
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Figure 2: Reduction in CMV load in the blood of five AIDS retinitis patients subjected to intensive sampling after initiation of intravenous GCV therapy. The data points are represented as filled circles, and the computed line of best fit is shown.

Mentions: Further refinement of the half-life of decline of CMV DNA in blood was achieved by enrolling five AIDS patients with CMV retinitis into an intravenous GCV induction study that involved frequent sampling (median of five samples per patient over 21 d of therapy). The CMV load modulations in these patients are shown in Fig. 2, together with the slope of decline of viral load. The average half-life of decline of CMV in the blood of these patients was 0.98 ± 0.3 d. A similar estimate was obtained for the decline of CMV DNA in the urine (0.96 ± 0.14 d; data not shown). The advantage of performing these detailed studies in the HIV-infected host relates to their relatively stable CMV DNA load (mean difference between samples before therapy 0.2 log10 genomes/ml) in the month preceding therapy, i.e., they fulfill the requirement for a steady state to be present at the initiation of therapy.


The dynamics of human cytomegalovirus replication in vivo.

Emery VC, Cope AV, Bowen EF, Gor D, Griffiths PD - J. Exp. Med. (1999)

Reduction in CMV load in the blood of five AIDS retinitis patients subjected to intensive sampling after initiation of intravenous GCV therapy. The data points are represented as filled circles, and the computed line of best fit is shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195570&req=5

Figure 2: Reduction in CMV load in the blood of five AIDS retinitis patients subjected to intensive sampling after initiation of intravenous GCV therapy. The data points are represented as filled circles, and the computed line of best fit is shown.
Mentions: Further refinement of the half-life of decline of CMV DNA in blood was achieved by enrolling five AIDS patients with CMV retinitis into an intravenous GCV induction study that involved frequent sampling (median of five samples per patient over 21 d of therapy). The CMV load modulations in these patients are shown in Fig. 2, together with the slope of decline of viral load. The average half-life of decline of CMV in the blood of these patients was 0.98 ± 0.3 d. A similar estimate was obtained for the decline of CMV DNA in the urine (0.96 ± 0.14 d; data not shown). The advantage of performing these detailed studies in the HIV-infected host relates to their relatively stable CMV DNA load (mean difference between samples before therapy 0.2 log10 genomes/ml) in the month preceding therapy, i.e., they fulfill the requirement for a steady state to be present at the initiation of therapy.

Bottom Line: The results from all three approaches demonstrated that the doubling time/half-life of CMV in blood is approximately 1 d when frequent samples are collected.These results show that CMV DNA replication in vivo is a highly dynamic process.We conclude that the reputation of CMV as a slowly replicating virus based on the time taken to produce cytopathic effects in vitro is unwarranted.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Royal Free and University College Medical School of University College London, London NW3 2QG, United Kingdom. vincent@rfhsm.ac.uk

ABSTRACT
Cytomegalovirus (CMV) is generally described as a slowly replicating virus. During studies of immunocompromised patients, we observed rapid changes in the quantity of CMV DNA present in serial blood samples by quantitative-competitive polymerase chain reaction commensurate with a doubling time of <2 d. To further investigate the dynamics of replication in vivo, patients in three distinct situations were studied in detail: (a) those receiving intravenous ganciclovir; (b) those in whom ganciclovir-resistant strains appeared during long-term therapy; and (c) those in whom ganciclovir-resistant strains disappeared with alternative drug therapy. In all cases, it was possible to provide accurate estimates of the doubling time of CMV and its half-life of disappearance after antiviral chemotherapy. The results from all three approaches demonstrated that the doubling time/half-life of CMV in blood is approximately 1 d when frequent samples are collected. These results show that CMV DNA replication in vivo is a highly dynamic process. We conclude that the reputation of CMV as a slowly replicating virus based on the time taken to produce cytopathic effects in vitro is unwarranted. These findings have implications for the potency, dose, and duration of antiviral chemotherapy needed for the effective treatment of this important human pathogen.

Show MeSH
Related in: MedlinePlus