The dynamics of human cytomegalovirus replication in vivo.
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.
Emery
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VC
Department of Virology, Royal Free and University College Medical School of University College London, London NW3 2QG, United Kingdom. vincent@rfhsm.ac.uk
Cope
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AV
Bowen
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EF
Gor
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Griffiths
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PD
D000998:Antiviral Agents / Q000627:therapeutic use; D001483:Base Sequence; D003587:Cytomegalovirus / Q000187:drug effects / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000821:virology*; D017931:DNA Primers / Q000235:genetics; D004261:DNA Replication / Q000187:drug effects / Q000502:physiology; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D004352:Drug Resistance, Microbial; D015774:Ganciclovir / Q000627:therapeutic use; D005814:Genes, Viral; D006801:Humans; D007700:Kinetics; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
D000998:Antiviral Agents; D017931:DNA Primers; D004279:DNA, Viral; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D015774:Ganciclovir