Mutations in the cytomegalovirus UL97 gene associated with ganciclovir resistance in recipients of allogeneic hematopoietic stem cell transplants

Clinical Microbiology and Antimicrobial Chemotherapy. 2019; 21(4):352-357

​ Demin M.V., Tikhomirov D.S., Biderman B.V., Glinshchikova O.A., Drokov M.Yu., Sudarikov A.B., Tupoleva T.A., Filatov F.P.
10.36488/cmac.2019.4.352-357
cytomegalovirus allogeneic hematopoietic stem cell transplantation mutation antiviral resistance ganciclovir
Section
Personal Experience
Type
Original Article
Publication
Clinical Microbiology and Antimicrobial Chemotherapy. 2019; 21(4):352-357

Objective.

To identify mutations in UL97 gene associated with antiviral drug resistance in recipients of allogeneic hematopoietic stem cells transplants (allo-HSCT).

Materials and Methods.

A total of 9 HCMV DNA samples were studied. These samples were received from the blood of 8 allo-HSCT recipients who were infected with HCMV and undergoing treatment at NMRC of Hematology (Russia) over the period of 2016 to 2017. Sanger sequencing was used to find mutations. The sequenced part of the virus DNA was analyzed using nucleotide BLAST and Genome compiler. Mutations were identified using MRA program which compared the obtained nucleotide sequence with the reference sequence of UL97 gene from Merlin strain.

Results.

Rate of detection of viruses with mutations that may lead to drug resistance is relatively high – 3 of 8 patients. The following mutations were identified: C592G, C607F and C603W. The obtained data shows that the presence and characteristics of mutations affect the viral load and the time when HCMV DNA is identified in blood.

Conclusions.

Obtained data show that presence of mutations impacts the course infection, leading to higher viral load and longer persistence of viral DNA in blood samples. Identified mutations had different resistance factor, which also impacted on the pattern of infection.

Mikhail V. Demin

National Medical Research Center of Hematology, Moscow, Russia

Tikhomirov D.S.

National Medical Research Center of Hematology, Moscow, Russia

Biderman B.V.

National Medical Research Center of Hematology, Moscow, Russia

Glinshchikova O.A.

National Medical Research Center of Hematology, Moscow, Russia

Drokov M.Yu.

National Medical Research Center of Hematology, Moscow, Russia

Sudarikov A.B.

National Medical Research Center of Hematology, Moscow, Russia

Tupoleva T.A.

National Medical Research Center of Hematology, Moscow, Russia

Filatov F.P.

I.I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia
N.F. Gamaleya National Research Center of Epidemiology and Microbiology, Moscow, Russia

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