Phenotype and Genotype Study of Novel C480F Maribavir-Ganciclovir Cross-Resistance Mutation Detected in Hematopoietic Stem Cell and Solid Organ Transplant Recipients

2021 ◽  
Author(s):  
Marta Santos Bravo ◽  
Nicolas Plault ◽  
Sonsoles Sánchez Palomino ◽  
María Mar Mosquera Gutierrez ◽  
Francesc Fernández Avilés ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Organ Transplant ◽  
Resistance Mutation ◽  
Cross Resistance ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Ganciclovir Treatment

Abstract Two transplant recipients (1 kidney and 1 hematopoietic stem cell) received maribavir (MBV) after cytomegalovirus (CMV) infection clinically resistant to standard therapy. Both patients achieved CMV DNA clearance within 30 and 18 days; however, the UL97 C480F variant emerged, causing recurrent CMV infection after a cumulative 2 months of MBV and 15 or 4 weeks of ganciclovir treatment, respectively. C480F was not detected under ganciclovir before MBV treatment. Recombinant phenotyping showed that C480F conferred the highest level of MBV resistance and ganciclovir cross-resistance, with impaired viral growth. Clinical follow-up and genotypic and phenotypic studies are essential for the assessment and optimization of patients with suspected MBV resistance.

scholarly journals Beyond Cytomegalovirus and Epstein-Barr Virus: a Review of Viruses Composing the Blood Virome of Solid Organ Transplant and Hematopoietic Stem Cell Transplant Recipients

2020 ◽  
Vol 33 (4) ◽  
Author(s):  
Marie-Céline Zanella ◽  
Samuel Cordey ◽  
Laurent Kaiser
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Clinical Significance ◽  
Viral Infections ◽  
Solid Organ Transplantation ◽  
High Morbidity ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Stem

SUMMARY Viral primary infections and reactivations are common complications in patients after solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) and are associated with high morbidity and mortality. Among these patients, viral infections are frequently associated with viremia. Beyond the usual well-known viruses that are part of the routine clinical management of transplant recipients, numerous other viral signatures or genomes can be identified in the blood of these patients. The identification of novel viral species and variants by metagenomic next-generation sequencing has opened up a new field of investigation and new paradigms. Thus, there is a need to thoroughly describe the state of knowledge in this field with a review of all viral infections that should be scrutinized in high-risk populations. Here, we review the eukaryotic DNA and RNA viruses identified in blood, plasma, or serum samples of pediatric and adult SOT/HSCT recipients and the prevalence of their detection, with a particular focus on recently identified viruses and those for which their potential association with disease remains to be investigated, such as members of the Polyomaviridae, Anelloviridae, Flaviviridae, and Astroviridae families. Current knowledge of the clinical significance of these viral infections with associated viremia among transplant recipients is also discussed. To ensure a comprehensive description in these two populations, individuals described as healthy (mostly blood donors) are considered for comparative purposes. The list of viruses that should be on the clinicians’ radar is certainly incomplete and will expand, but the challenge is to identify those of possible clinical significance.

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