期刊
DRUG RESISTANCE UPDATES
卷 37, 期 -, 页码 1-16出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.drup.2018.01.003
关键词
Thymidine kinase; Protein kinase; Herpesviruses; Drug-resistance; Mutations; Nucleos(t)ide analogues
Herpesviruses thymidine kinase (TIC) and protein kinase (PK) allow the activation of nucleoside analogues used in anti-herpesvirus treatments. Mutations emerging in these two genes often lead to emergence of drug-resistant strains responsible for life-threatening diseases in immunocompromised populations. In this review, we analyze the binding of different nucleoside analogues to the TK active site of the three a-herpesviruses [Herpes Simplex Virus 1 and 2 (HSV-1 and HSV-2) and Varicella-Zoster Virus (VZV)] and present the impact of known mutations on the structure of the viral TKs. Furthermore, models of P-herpesviruses [Human cytomegalovirus (HCMV) and human herpesvirus-6 (HHV-6)] PKs allow to link amino acid changes with resistance to ganciclovir and/or maribavir, an investigational chemotherapeutic used in patients with multidrug-resistant HCMV. Finally, we set the basis for the understanding of drug-resistance in gamma-herpesviruses [Epstein-Barr virus (EBV) and Kaposi's sarcoma associated herpesvirus (KSHV)] TIC and PK through the use of animal surrogate models.
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