ABSTRACT
Immunocompromised patients, including hematopoietic stem cell transplantation (HSCT), HIV, and malnourished patients, are at increased risk for viral infections with high incidences of morbidity and mortality. In HSCT patients, the infection risk is increased until immune reconstitution is re-established. Therapy with standard of care antiviral drugs, for example Cidofovir, is expensive, requires prolonged administration, and has unfavorable toxicity profiles. Our case describes the successful use of Brincidofovir (CMX001), a lipid-conjugate of the nucleotide analog Cidofovir, in a 9-year-old post-HSCT girl with disseminated adenovirus infection. The increased efficacy of Brincidofovir (BCV) against multiple viral infections, limited toxicity, and oral-administered schedule opens options in different resource settings.
ABSTRACT
The thy- mutator phenotype of Chinese hamster ovary cells is distinguished by increased intracellular levels of dCTP, auxotrophy for thymidine, and elevated spontaneous mutational rates. To determine the biochemical lesion responsible for this complex phenotype, enzymes responsible for the synthesis of dCTP and dTTP were investigated. Levels of ribonucleotide reductase and dCMP deaminase were identical in mutant and wild type strains. In contrast, CTP synthetase activity in extracts from thy- strains was consistently altered in that 50% of enzyme activity was resistant to feedback inhibition by CTP. Additionally, thy- strains obtained by DNA transfection also had CTP-resistant CTP synthetase. Thy+ revertants lost the resistant enzyme, and total activity was reduced. CTP-resistant CTP synthetase was regained in thy- mutants reselected from thy+ revertants, but in these strains all activity was resistant. These experiments demonstrate that the thy- mutator phenotype is a consequence of a mutation of CTP synthetase and suggest that one pathway of reversion to the wild type state is by loss or inactivation of the mutant allele rendering the revertants hemizygous for the gene.
