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Mutations in Human Cytymegalovirus (orthoherpesviridae: Herpesvirales: Cytomegalovirus: Cytomegalovirus Humanbeta 5) UL97 Gene Lead to Increase in Viremia Duration and Poor Antiviral Response in Recipients of Allogeneic Hematopoietic Stem Cells

Dmitriy S. Tikhomirov, Mikhail V. Demin, Anastasia A. Serikova,Bella V. Biderman,Andrey B. Sudarikov, Felix P. Filatov,Tatiana A. Tupoleva

Problems of Virology(2024)

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Abstract
Introduction. Human cytomegalovirus (Orthoherpesviridae: Herpesvirales: Cytomegalovirus: Cytomegalovirus humanbeta 5) (HCMV) is one of the most commonly detected viruses in recipients of allogeneic hematopoietic stem cell (allo-HSCT) transplants. However, the emergence of resistance to antiviral drugs such as ganciclovir (GCV) poses a challenge in managing these patients. This study aims to investigate the prevalence and impact of mutations in the HCMV UL97 gene associated with resistance to GCV on the course of infection among allo-HSCT patients. Materials and methods. The study examined the association between UL97 mutations and the clinical course of HCMV infection in allo-HSCT patients. Genetic sequencing was performed to identify mutations, and their impact on viral replication and resistance to GCV was assessed. Results and discussion. Six mutations were identified (D490A, T502A, C592G, C592F, E596G, C603W). C592G, C592F, E596G, and C603W are associated with resistance to antiviral drugs, while D490A and T502A described for the first time. When comparing patients with wild-type and those carrying the mutant variant, several parameters of peripheral blood were significantly lower in the former group. The median time to peak viral load following allo-HSCT, duration of viremia, and rate of virological response to high-dose therapy also differed significantly between the two groups. Conclusion. It was shown that approximately one third (4 out of 14) of allogeneic stem cell transplant recipients had mutations associated with resistance to GCV. Patients carrying the mutant variant of HCMV had longer viremia and took longer to achieve a negative virological test result after starting high-dose therapy. Performing genotyping may help make more evidence-based therapeutic decisions.
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要点】:研究揭示了人巨细胞病毒UL97基因突变与抗病毒药物耐药性之间的关系,及其对造血干细胞移植受者感染过程的影响。

方法】:通过遗传测序分析UL97基因突变,评估其对病毒复制和对抗病毒药物如更昔洛韦的耐药性影响。

实验】:在allo-HSCT患者中识别出六种UL97基因突变,并通过比较野生型与突变型患者在病毒载量高峰时间、病毒血症持续时长及对高剂量治疗病毒学反应率等参数上的差异,得出突变型患者病毒血症时间更长,治疗反应更慢的结果。数据集未在文本中明确提及。