Biomaterial Database

Mechanisms of inhibition of herpes simplex virus type 2 growth by 28-mer phosphorothioate oligodeoxycytidine. 1990

W Y Gao, and J W Jaroszewski, and J S Cohen, and Y C Cheng

Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.

The 28-mer phosphorothioate oligodeoxycytidine (S-(dC)28) has been reported previously to be a strong inhibitor of herpes simplex virus type 2 (HSV-2) DNA polymerase and HSV-2 growth in cell culture. In this study, the mechanism of action of S-(dC)28 was studied. S-(dC)28 was found to interfere with the adsorption of HSV-1 and HSV-2 to HeLa cells. HSV-2 infection, but not HSV-1, was found to potentiate the uptake of S-(dC)28 into HeLa cells. The enhanced uptake reached a plateau at 6-9 h postinfection and appeared to be dose-dependent and saturable at concentrations higher than 1 microM. The amount of S-(dC)28 accumulated in HSV-2 infected cells was found to be 50 pmol/10(6) cells at 6 h postinfection, whereas no significant drug accumulation was found in uninfected cells. S-(dC)28 binding studies suggested that there are several types of tight binding sites associated with HSV-2 virions, which could play a role in the enhancement of S-(dC)28 uptake. Subcellular distribution studies showed that intracellular S-(dC)28 was associated with both nuclei and cytoplasm and remained intact. Mechanism studies suggested three different mechanisms which could be responsible for the anti-HSV-2 action of S-(dC)28; (i) S-(dC)28 could interfere with the uptake of HSV. (ii) HSV-2 infection enhances the uptake of S-(dC)28 into cells. (iii) S-(dC)28 inhibits HSV-2 DNA synthesis, possibly, by inhibiting the viral DNA polymerase. The unique mechanisms of anti-HSV action of S-(dC)28 suggest it could be a potential new agent in anti-HSV-2 chemotherapy.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D009838	Oligodeoxyribonucleotides	A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.	Oligodeoxynucleotide,Oligodeoxyribonucleotide,Oligodeoxynucleotides
D002467	Cell Nucleus	Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)	Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D003593	Cytoplasm	The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)	Protoplasm,Cytoplasms,Protoplasms
D003851	Deoxyribonucleases	Enzymes which catalyze the hydrolases of ester bonds within DNA. EC 3.1.-.	DNAase,DNase,Deoxyribonuclease,Desoxyribonuclease,Desoxyribonucleases,Nucleases, DNA,Acid DNase,Alkaline DNase,DNA Nucleases,DNase, Acid,DNase, Alkaline
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
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D006367	HeLa Cells	The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays.	Cell, HeLa,Cells, HeLa,HeLa Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man