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Ganciclovir-resistant cytomegalovirus clinical isolates: mode of resistance to ganciclovir. 1991

S C Stanat, and J E Reardon, and A Erice, and M C Jordan, and W L Drew, and K K Biron
Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.

Cytomegalovirus strains with reduced in vitro susceptibilities to ganciclovir have been recovered from patients who failed long-term ganciclovir therapy. The ganciclovir-resistant clinical isolates in this study were unable to induce ganciclovir phosphorylation in virus-infected cells. The viral DNA polymerase function appeared unaltered in one genetically pure ganciclovir-resistant strain, compared with that of its wild-type ganciclovir-sensitive counterpart. All nine of the ganciclovir-resistant strains were susceptible to foscarnet. Moreover, these strains were sensitive to inhibition both by vidarabine and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC), antiviral agents that are activated by cellular enzymes, and by (S)-1(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), which is a monophosphate nucleoside analog. The in vitro resistance to ganciclovir of the ganciclovir-resistant clinical isolates studied was attributed to the inability of the cells infected with these isolates to phosphorylate ganciclovir; the virally encoded DNA polymerase did not appear to play a role in this ganciclovir resistance.

UI MeSH Term Description Entries
D010948 Viral Plaque Assay Method for measuring viral infectivity and multiplication in CULTURED CELLS. Clear lysed areas or plaques develop as the VIRAL PARTICLES are released from the infected cells during incubation. With some VIRUSES, the cells are killed by a cytopathic effect; with others, the infected cells are not killed but can be detected by their hemadsorptive ability. Sometimes the plaque cells contain VIRAL ANTIGENS which can be measured by IMMUNOFLUORESCENCE. Bacteriophage Plaque Assay,Assay, Bacteriophage Plaque,Assay, Viral Plaque,Assays, Bacteriophage Plaque,Assays, Viral Plaque,Bacteriophage Plaque Assays,Plaque Assay, Bacteriophage,Plaque Assay, Viral,Plaque Assays, Bacteriophage,Plaque Assays, Viral,Viral Plaque Assays
D003586 Cytomegalovirus Infections Infection with CYTOMEGALOVIRUS, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. CMV Inclusion,CMV Inclusions,Congenital CMV Infection,Congenital Cytomegalovirus Infection,Cytomegalic Inclusion Disease,Cytomegalovirus Colitis,Cytomegalovirus Inclusion,Cytomegalovirus Inclusion Disease,Cytomegalovirus Inclusions,Inclusion Disease,Perinatal CMV Infection,Perinatal Cytomegalovirus Infection,Renal Tubular Cytomegalovirus Inclusion,Renal Tubular Cytomegalovirus Inclusions,Salivary Gland Virus Disease,Severe Cytomegalovirus Infection,Severe Cytomegalovirus Infections,Infections, Cytomegalovirus,CMV Infection, Congenital,CMV Infection, Perinatal,Colitis, Cytomegalovirus,Congenital CMV Infections,Congenital Cytomegalovirus Infections,Cytomegalic Inclusion Diseases,Cytomegalovirus Colitides,Cytomegalovirus Inclusion Diseases,Cytomegalovirus Infection,Cytomegalovirus Infection, Congenital,Cytomegalovirus Infection, Perinatal,Cytomegalovirus Infection, Severe,Cytomegalovirus Infections, Severe,Disease, Cytomegalic Inclusion,Disease, Cytomegalovirus Inclusion,Diseases, Cytomegalovirus Inclusion,Inclusion Disease, Cytomegalic,Inclusion Disease, Cytomegalovirus,Inclusion Diseases,Inclusion Diseases, Cytomegalovirus,Inclusion, CMV,Inclusion, Cytomegalovirus,Infection, Congenital CMV,Infection, Congenital Cytomegalovirus,Infection, Cytomegalovirus,Infection, Perinatal CMV,Infection, Perinatal Cytomegalovirus,Infection, Severe Cytomegalovirus,Perinatal CMV Infections,Perinatal Cytomegalovirus Infections
D003587 Cytomegalovirus A genus of the family HERPESVIRIDAE, subfamily BETAHERPESVIRINAE, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. Herpesvirus 5, Human,Human Herpesvirus 5,Salivary Gland Viruses,HHV 5,Herpesvirus 5 (beta), Human,Cytomegaloviruses,Salivary Gland Virus,Virus, Salivary Gland,Viruses, Salivary Gland
D004259 DNA-Directed DNA Polymerase DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair. DNA Polymerase,DNA Polymerases,DNA-Dependent DNA Polymerases,DNA Polymerase N3,DNA Dependent DNA Polymerases,DNA Directed DNA Polymerase,DNA Polymerase, DNA-Directed,DNA Polymerases, DNA-Dependent,Polymerase N3, DNA,Polymerase, DNA,Polymerase, DNA-Directed DNA,Polymerases, DNA,Polymerases, DNA-Dependent DNA
D004261 DNA Replication The process by which a DNA molecule is duplicated. Autonomous Replication,Replication, Autonomous,Autonomous Replications,DNA Replications,Replication, DNA,Replications, Autonomous,Replications, DNA
D004279 DNA, Viral Deoxyribonucleic acid that makes up the genetic material of viruses. Viral DNA
D004352 Drug Resistance, Microbial The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS). Antibiotic Resistance,Antibiotic Resistance, Microbial,Antimicrobial Resistance, Drug,Antimicrobial Drug Resistance,Antimicrobial Drug Resistances,Antimicrobial Resistances, Drug,Drug Antimicrobial Resistance,Drug Antimicrobial Resistances,Drug Resistances, Microbial,Resistance, Antibiotic,Resistance, Drug Antimicrobial,Resistances, Drug Antimicrobial
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000163 Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral

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