Razonable Raymund R
Division of Infectious Diseases, William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.
Curr Opin Organ Transplant. 2018 Aug;23(4):388-394. doi: 10.1097/MOT.0000000000000541.
Cytomegalovirus (CMV) infection can be refractory to antiviral treatment. Although refractoriness can be due impaired host immunity, it can also be due to viral mutations that confer antiviral drug resistance. This article provides a succinct review of mutations in CMV genes that confer drug resistance, and offer guidance on clinical management.
Recent advances in medical and research technology have confirmed traditional mutations and identified novel ones that confer resistance to current antiviral drugs. Resistance to ganciclovir is commonly predicted by mutations in UL97, which encode for viral kinase that catalyzes its phosphorylation. Mutations in UL54, which encode for CMV DNA polymerase, confer resistance (or cross-resistance) to ganciclovir, cidofovir and/or foscarnet. Resistance to letermovir, the new drug approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients, has emerged and mapped most commonly to mutations in UL56 and less commonly UL51 and UL89, the gene complex that encode for viral terminase.
Mutations in CMV genes can be selected during antiviral drug exposure, and manifests phenotypically as nonresponsive drug-resistant disease. Knowledge of specific mutations informs clinicians in selecting appropriate antivirals for managing transplant patients with CMV disease.
巨细胞病毒（CMV）感染对抗病毒治疗可能具有难治性。难治性可能是由于宿主免疫功能受损，但也可能是由于病毒发生突变而产生抗病毒药物耐药性。本文简要综述了CMV基因中导致耐药性的突变情况，并为临床管理提供指导。
医学和研究技术的最新进展证实了传统的突变，并发现了导致对当前抗病毒药物耐药的新突变。对更昔洛韦的耐药性通常由UL97基因的突变预测，该基因编码催化其磷酸化的病毒激酶。编码CMV DNA聚合酶的UL54基因发生突变，会导致对更昔洛韦、西多福韦和/或膦甲酸钠产生耐药性（或交叉耐药性）。对来特莫韦（已被批准用于异基因造血干细胞移植受者的CMV预防的新药）的耐药性已经出现，最常见的是UL56基因发生突变，较少见的是UL51和UL89基因发生突变，这两个基因共同编码病毒末端酶。
CMV基因中的突变可在抗病毒药物治疗期间产生，其表型表现为对药物无反应的耐药性疾病。了解特定的突变有助于临床医生为治疗CMV疾病的移植患者选择合适的抗病毒药物。
