Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients

Computational and Structural Biotechnology Journal
Katharina GöhringGerhard Jahn

Abstract

In pediatric and adult patients after stem cell transplantation (SCT) disseminated infections caused by human cytomegalovirus (HCMV) can cause life threatening diseases. For treatment, the three antivirals ganciclovir (GCV), foscarnet (PFA) and cidofovir (CDV) are approved and most frequently used. Resistance to all of these antiviral drugs may induce a severe problem in this patient cohort. Responsible for resistance phenomena are mutations in the HCMV phosphotransferase-gene (UL97) and the polymerase-gene (UL54). Most frequently mutations in the UL97-gene are associated with resistance to GCV. Resistance against all three drugs is associated to mutations in the UL54-gene. Monitoring of drug resistance by genotyping is mostly done by PCR-based Sanger sequencing. For phenotyping with cell culture the isolation of HCMV is a prerequisite. The development of multidrug resistance with mutation in both genes is rare, but it is often associated with a fatal outcome. The manifestation of multidrug resistance is mostly associated with combined UL97/UL54-mutations. Normally, mutations in the UL97 gene occur initially followed by UL54 mutation after therapy switch. The appearance of UL54-mutation alone without any detection of UL97-mutat...Continue Reading

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Citations

Dec 18, 2015·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Marco HerlingVeronica Di Cristanziano
Apr 12, 2016·International Journal of Pediatric Otorhinolaryngology·Douglas SidellDaniel I Choo
Jun 21, 2015·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·J LiuX J Huang
Apr 5, 2016·Expert Review of Hematology·Enrico MaffiniBenedetto Bruno
Apr 14, 2017·Intervirology·Azam MirarabAlijan Tabarraei
Mar 17, 2018·Antiviral Chemistry & Chemotherapy·Koh-Hei YamadaNaoki Inoue
May 17, 2018·Revista Da Sociedade Brasileira De Medicina Tropical·Dorotéa de Fátima Lobato da SilvaRita Catarina Medeiros Sousa
Oct 1, 2019·Current Opinion in Infectious Diseases·Fareed KhawajaRoy F Chemaly
Apr 17, 2019·International Journal of Molecular Sciences·Tanja BeckerMirko Trilling
Oct 8, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Georgios PapadakisNicole Pouli

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Methods Mentioned

BETA
phosphotransferase
PCR
electrophoresis

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