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J Infect Dis. 1996 Sep;174(3):476-82.

Spontaneous reactivation of thymidine kinase-deficient, acyclovir-resistant type-2 herpes simplex virus: masked heterogeneity or reversion?

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Division of Infectious Diseases, Department of Medicine, University of British Columbia, Vancouver, Canada.


Herpes simplex virus (HSV) strain 1737, acyclovir-resistant and uniformly thymidine kinase-deficient (tkD) by all conventional assays, clinically reactivated in an AIDS patient in the absence of antiviral drug pressure. Investigation of its neurovirulence and latency characteristics in a mouse model using a tkD plaque isolate (1737-14), however, yielded a neurovirulent, homogeneous, acyclovir-sensitive, tk wild type (tkWT) strain (1737-14ME), while trigeminal ganglia from a surviving animal yielded a heterogeneous tkD/tkWT population (1737-14/10(5)B). Heterogeneity may have arisen due to selection of a preexisting tkWT subpopulation or to genetic reversion. "Ultralow" levels of tk, undetectable by conventional means, may be sufficient for reactivation while retaining the acyclovir-resistant phenotype. A possible mechanism for spontaneous reactivation of 1737 is in vivo complementation between heterogeneous tk populations. Eradication of acyclovir-resistant, tkD virus does not ensure subsequent reactivations to be acyclovir-sensitive, and alternating antivirals may be required for effective therapy.

[Indexed for MEDLINE]

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