Genital herpes due to acyclovir-sensitive herpes simplex virus caused secondary and recurrent herpetic whitlows due to thymidine kinase-deficient/temperature-sensitive virus.

Herpes simplex virus (HSV)-2 caused a genital ulcer in a 40-year-old allogenic stem cell recipient, and a secondary herpetic whitlow appeared during 2 months of acyclovir (ACV) therapy. Both genital ulcer, and whitlow were cured 3 months later, but 6 months after recovery the whitlow alone recurred. DNA of the genital, first, and recurrent whitlow isolates showed similar endonuclease digestion fragment profiles. The genital virus was ACV-sensitive, and the two whitlow isolates were ACV-resistant/thymidine kinase (TK)-deficient. The TK gene of the whitlow isolates had the same frame shift from the 274th amino acid and termination at the 347th amino acid due to the deletion of a cytosine at the 819th nucleotide. Because the temperature of the thumb is 33/34 degrees C or lower, the temperature sensitivity of the isolates were compared, and both whitlow isolates were significantly more temperature-sensitive (ts) at 39 degrees C than the genital isolate. The two whitlow isolates showed cutaneous pathogenicity in mouse ear pinna but not midflank, while the genital isolate was pathogenic at both sites, suggesting that temperature adaptation was an important element of pathogenicity in the whitlow. The virus populations of isolates of the genital, and first whitlow were examined by 31, and 82 clones, respectively, and the clones from genital, and whitlow isolates were ACV-sensitive, and -resistant, respectively, showing their homogeneity. The acyclovir-sensitive genital lesion had spread as a TK-deficient/ts herpetic whitlow during ACV treatment, and an apparently TK-deficient virus adapted to the local temperature might have caused the whitlow recurrence.