Human cytomegalovirus antiviral drug resistance in hematopoietic stem cell transplantation: current state of the art

被引:50
作者
Campos, Ana Bela [1 ,3 ]
Ribeiro, Joana [1 ,2 ,3 ]
Boutolleau, David [4 ,5 ,6 ]
Sousa, Hugo [1 ,2 ]
机构
[1] CI IPOP, Mol Oncol & Viral Pathol Grp, Porto, Portugal
[2] Portuguese Oncol Inst Porto, Virol Serv, Porto, Portugal
[3] Univ Porto, Fac Med, Rua Campo Alegre 823, P-4100 Porto, Portugal
[4] Univ Paris 06, Sorbonne Univ, CIMI Paris, CR7, Paris, France
[5] INSERM, CIMI Paris, U1135, Paris, France
[6] Hop Univ La Pitie Salpetriere Charles Foix, AP HP, Serv Virol, Paris, France
关键词
DNA-POLYMERASE MUTATIONS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CONFERRING GANCICLOVIR RESISTANCE; UL97 PHOSPHOTRANSFERASE MUTATIONS; BONE-MARROW-TRANSPLANTATION; COMPOUND AIC246 LETERMOVIR; IMMUNOCOMPROMISED PATIENTS; CMV INFECTION; MULTIDRUG-RESISTANCE; IN-VITRO;
D O I
10.1002/rmv.1873
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant recipients. The significant clinical impact of HCMV infection and progression to HCMV disease among allogeneic hematopoietic stem cell transplant recipients has been reduced by prophylactic, preemptive, and curative treatments using ganciclovir, valganciclovir, foscarnet, and cidofovir. Resistance to (val)ganciclovir results from mutations localized in HCMV UL97 gene (encoding the pUL97 phosphotransferase), UL54 gene (encoding the pUL54 DNA polymerase), or both genes, whereas foscarnet and cidofovir resistance results from mutations localized within UL54 gene only. This review is focused on HCMV antiviral drug resistance, including the functions of target genes of antivirals, the mechanisms of antiviral resistance, the different mutations in pUL97 and pUL54 that have been identified in either clinical isolates or laboratory strains, and their impact on HCMV susceptibility to antiviral drugs. It emphasizes the importance of proving that observed genetic changes confer resistance so they can be distinguished from polymorphisms. Because of the emergence of HCMV resistance to currently available drugs, novel drugs are urgently needed for the therapeutic management of HCMV-resistant infections in hematopoietic stem cell transplant patients. Copyright (c) 2016 John Wiley & Sons, Ltd.
引用
收藏
页码:161 / 182
页数:22
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