Molecular analysis of human cytomegalovirus strains from two lung transplant recipients with the same donor

A total of four cytomegalovirus (CMV) isolates were obtained from two CMV seronegative patients, each of whom received a lung transplant from the same serepositive donor. CMV was isolated from Patient 1 from two bronchial alveolar lavage (BAL) specimens, one obtained during treatment with ganciclovir (GCV) and a second during later treatment with foscarnet. Both of these isolates are sensitive to GCV and foscarnet. CMV was isolated from Patient 2 from a blood and a BAL specimen obtained during treatment with GCV. Both of these isolates are resistant to GCV and show reduced GCV phosphorylation. Patient 1 is still alive 33 months posttransplant. Patient 2 died 6 1/2 months posttransplant. Although the four strains differ with respect to GCV susceptibility and phosphorylation, their DNA restriction fragment hybridization patterns and UL97 kinase gene sequences indicate that they are closely related. The restriction fragment hybridization patterns are identical among the strains, while these patterns differ markedly from those of unrelated strains. The DNA sequences of the UL97 genes of the strains from Patient 2 differ by only one nucleotide from those of Patient 1. The same comparison with unrelated strains shows a minimum of 12 nucleotide differences. The nucleotide change in the strains from Patient 2 produces all amino acid substitution of serine for leucine at residue 595, a substitution that was previously shown to transfer GCV resistance. Both patients, therefore, were apparently infected with the same donor strain, but during the course of GCV prophylaxis and treatment, a GCV-resistant mutant strain was selected in Patient 2.