Antiviral drug resistance. 1990

D M Coen
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.

Antiviral drug resistance is an area of increasing importance in acquired immunodeficiency syndrome (AIDS), not only in terms of the human immunodeficiency virus (HIV), but also opportunistic pathogens such as herpes simplex virus (HSV) and human cytomegalovirus (CMV). Studies of drug resistance in these and other viruses have proven valuable both for the molecular dissection of drug mechanisms and drug targets and for predicting the features of drug resistance in clinical settings: Drug-resistance mutations arise readily, due in part to a lack of fidelity of viral polymerase. Both biochemical and genetic analyses are generally required to understand the basis of drug resistance. Novel drug targets, such as a CMV gene product that contributes to ganciclovir phosphorylation, can be identified by analysis of such mutations. Regions of drug targets that are involved in drug recognition can be identified by sequencing of drug-resistance mutations. Analysis of drug-resistant viruses, obtained either in the laboratory or from patients, reveals a broad spectrum of alterations and points to the importance of heterogeneous populations of virus in resistance and pathogenesis.

UI MeSH Term Description Entries
D007108 Immune Tolerance The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. Immunosuppression (Physiology),Immunosuppressions (Physiology),Tolerance, Immune
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
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
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
D006564 Herpesviridae A family of enveloped, linear, double-stranded DNA viruses infecting a wide variety of animals. Subfamilies, based on biological characteristics, include: ALPHAHERPESVIRINAE; BETAHERPESVIRINAE; and GAMMAHERPESVIRINAE. Mouse Thymic Virus,Murid herpesvirus 3,Thymic Group Viruses,Herpesviruses,Mouse Thymic Viruses,Thymic Virus, Mouse,Thymic Viruses, Mouse
D006678 HIV Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2. AIDS Virus,HTLV-III,Human Immunodeficiency Viruses,Human T-Cell Lymphotropic Virus Type III,Human T-Lymphotropic Virus Type III,LAV-HTLV-III,Lymphadenopathy-Associated Virus,Acquired Immune Deficiency Syndrome Virus,Acquired Immunodeficiency Syndrome Virus,Human Immunodeficiency Virus,Human T Cell Lymphotropic Virus Type III,Human T Lymphotropic Virus Type III,Human T-Cell Leukemia Virus Type III,Immunodeficiency Virus, Human,Immunodeficiency Viruses, Human,Virus, Human Immunodeficiency,Viruses, Human Immunodeficiency,AIDS Viruses,Human T Cell Leukemia Virus Type III,Lymphadenopathy Associated Virus,Lymphadenopathy-Associated Viruses,Virus, AIDS,Virus, Lymphadenopathy-Associated,Viruses, AIDS,Viruses, Lymphadenopathy-Associated
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
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
D012194 RNA-Directed DNA Polymerase An enzyme that synthesizes DNA on an RNA template. It is encoded by the pol gene of retroviruses and by certain retrovirus-like elements. EC 2.7.7.49. DNA Polymerase, RNA-Directed,RNA-Dependent DNA Polymerase,Reverse Transcriptase,RNA Transcriptase,Revertase,DNA Polymerase, RNA Directed,DNA Polymerase, RNA-Dependent,RNA Dependent DNA Polymerase,RNA Directed DNA Polymerase

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