ABSTRACT
A double-guanine-insertion mutation within a run of guanines in the herpes simplex virus gene encoding thymidine kinase (TK) was previously found in an acyclovir-resistant clinical isolate. This mutation was engineered into strain KOS, and stocks were generated from single plaques. Plaque autoradiography revealed that most plaques in such stocks exhibited low levels of TK activity, while ∼3% of plaques exhibited high levels of TK activity, indicating a remarkably high frequency of phenotypic reversion. This virus was able to reactivate from latency in mouse ganglia; a fraction of the reactivating virus expressed a high level of TK activity due to an additional G insertion, suggesting that the observed genetic instability contributed to pathogenicity.
FOOTNOTES
- Received 24 July 2002.
- Accepted 24 October 2002.
- ↵*Corresponding author. Mailing address: Dept. of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Ave., Boston, MA 02115. Phone: (617) 432-1691. Fax: (617) 432-3833. E-mail: Don_Coen{at}hms.harvard.edu.
- American Society for Microbiology
- Top
- Article
- ABSTRACT
- Construction of recombinant virus TKG7+2G.
- Heterogeneity of TK activity of virus carrying a double-G insertion.
- Enrichment of virus with high levels of TK activity during acute replication in the mouse.
- Reactivation from latency.
- What accounts for the low level of TK activity of most TKG7+2G plaques?
- What causes the high frequency of phenotypic reversion?
- ACKNOWLEDGMENTS
- FOOTNOTES
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