Enzymology and pathogenicity in mice of a herpes simplex virus type 1 mutant resistant to 2'-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-iodocytosine Journal Article
| Authors: | Colacino, J.; Brownridge, E.; Greenberg, N.; Lopez, C. |
| Article Title: | Enzymology and pathogenicity in mice of a herpes simplex virus type 1 mutant resistant to 2'-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-iodocytosine |
| Abstract: | The deoxypyrimidine nucleoside analog 2-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-iodocytosine (FIAC) is a potent and selective inhibitor of herpes simplex virus type 1 in vitro. Isopycnographic analysis demonstrated that 1 μM FIAC inhibited herpes simplex virus DNA replication by more than 95% but inhibited cellular DNA replication by only 32%. Mutant herpes simplex virus type 1 selected resistant to FIAC displayed linked resistance to other nucleoside analogs, including arabinosylthymine and acyclovir. Lysates derived from Vero cells infected with FIAC-resistant virus showed markedly lower levels of thymidine kinase activity and were unable to phosphorylate selectively arabinosylthymine or FIAC, in contrast to lysates from cells infected with wild-type herpes simplex virus type 1. Finally, drug-resistant virus displayed a 6,000-fold decrease in pathogenicity when inoculated intraperitoneally into genetically susceptible A/J mice. These results indicate that resistance to deoxypyrimidine nucleoside analogs is due, at least in part, to alterations in viral thymidine kinase and is accompanied by decreased pathogenicity in vivo. |
| Keywords: | unclassified drug; nonhuman; mouse; animal model; aciclovir; in vitro study; drug resistance; enzymology; cell culture; thymidine kinase; antivirus agent; virus infection; pathogenicity; radioisotope; herpes simplex virus 1; thymidine h 3; phosphonoacetic acid; virus mutation; experimental infection; intraperitoneal drug administration; 5 (2 bromovinyl) 2' deoxyuridine; clevudine; fiacitabine; priority journal; article; 2' fluoro 5 iodocytarabine c 14; thymine arabinoside |
| Journal Title: | Antimicrobial Agents and Chemotherapy |
| Volume: | 29 |
| Issue: | 5 |
| ISSN: | 0066-4804 |
| Publisher: | American Society for Microbiology |
| Date Published: | 1986-05-01 |
| Start Page: | 877 |
| End Page: | 882 |
| Language: | English |
| DOI: | 10.1128/aac.29.5.877 |
| PUBMED: | 3015008 |
| PROVIDER: | scopus |
| PMCID: | PMC284171 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 18 August 2021 -- Source: Scopus |
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