Virucidal activity of a GT-rich oligonucleotide against herpes simplex virus mediated by glycoprotein B.

Journal of Virology
Benjamin ShoganDonald M Coen

Abstract

We have investigated the antiviral mechanism of a phosphorothioate oligonucleotide, ISIS 5652, which has activity against herpes simplex virus (HSV) in the low micromolar range in plaque reduction assays. We isolated a mutant that is resistant to this compound. Marker rescue and sequencing experiments showed that resistance was due to at least one of three mutations in the UL27 gene which result in amino acid changes in glycoprotein B (gB). Because gB has a role in attachment and entry of HSV, we tested the effects of ISIS 5652 at these stages of infection. The oligonucleotide potently inhibited attachment of virus to cells at 4 degrees C; however, the resistant mutant did not exhibit resistance at this stage. Moreover, a different oligonucleotide with little activity in plaque reduction assays was as potent as ISIS 5652 in inhibiting attachment. Similarly, ISIS 5652 was able to inhibit entry of pre-attached virions into cells at 37 degrees C, but the mutant did not exhibit resistance in this assay. The mutant did not attach to or enter cells more quickly than did wild-type virus. Strikingly, incubation of wild-type virus with 1 to 2 microM ISIS 5652 at 37 degrees C led to a time-dependent, irreversible loss of infectivity (vir...Continue Reading

References

Jan 1, 1979·Cold Spring Harbor Symposia on Quantitative Biology·B RoizmanW T Ruyechan
Aug 1, 1991·Journal of Virology·S L HighlanderJ C Glorioso
Jul 1, 1988·The Journal of General Virology·D J McGeochP Taylor
May 1, 1964·Journal of Bacteriology·A J Nahmias, S Kibrick
Feb 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·J R WyattD J Ecker
Jan 1, 1994·Annual Review of Biophysics and Biomolecular Structure·J R Williamson
Aug 24, 2001·The Journal of Clinical Investigation·D Shukla, P G Spear
Dec 18, 2001·Biopolymers·R H Shafer, I Smirnov
Sep 13, 2003·Journal of Virology·Patricia G Spear, Richard Longnecker
Jan 1, 1998·Methods in Molecular Medicine·C A Maclean
Jan 1, 1998·Methods in Molecular Medicine·A R Maclean

❮ Previous
Next ❯

Citations

May 18, 2011·Antimicrobial Agents and Chemotherapy·Anna LuganiniGiorgio Gribaudo
Sep 15, 2010·Antimicrobial Agents and Chemotherapy·Suzanne J F KapteinJohan Neyts
Aug 18, 2010·Antimicrobial Agents and Chemotherapy·Beatrice MercorelliArianna Loregian
Jan 9, 2008·Antimicrobial Agents and Chemotherapy·Anna LuganiniGiorgio Gribaudo
Oct 18, 2013·BMC Complementary and Alternative Medicine·Manuela DonalisioDavid Lembo
May 17, 2011·Pharmacology & Therapeutics·Beatrice MercorelliArianna Loregian
Feb 27, 2013·Reviews in Medical Virology·Thessicar E AntoineDeepak Shukla
Dec 19, 2017·Nature Materials·Valeria CagnoFrancesco Stellacci
May 2, 2021·Research in Veterinary Science·Cristiana CatellaGianvito Lanave
Jun 15, 2021·Chemical Science·Md Waseem HussainAbhijit Patra

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.