Distribution and effects of amino acid changes in drug-resistant alpha and beta herpesviruses DNA polymerase

作者：Topalis D; Gillemot S; Snoeck R; Andrei G

来源：Nucleic Acids Research, 2016, 44(20): 9530-9554.

DOI：10.1093/nar/gkw875

Emergence of drug-resistance to all FDA-approved antiherpesvirus agents is an increasing concern in immunocompromised patients. Herpesvirus DNA polymerase (DNApol) is currently the target of nucleos(t)ide analogue-based therapy. Mutations in DNApol that confer resistance arose in immunocompromised patients infected with herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV), and to lesser extent in herpes simplex virus 2 (HSV-2), varicella zoster virus (VZV) and human herpesvirus 6 (HHV-6). In this review, we present distinct drug-resistant mutational profiles of herpesvirus DNApol. The impact of specific DNApol amino acid changes on drug-resistance is discussed. The pattern of genetic variability related to drug-resistance differs among the herpesviruses. Two mutational profiles appeared: one favoring amino acid changes in the Palm and Finger domains of DNApol (in alpha-herpesviruses HSV-1, HSV-2 and VZV), and another with mutations preferentially in the 3'-5' exonuclease domain (in beta-herpesvirus HCMV and HHV-6). The mutational profile was also related to the class of compound to which drug-resistance emerged.

• 出版日期2016-11
• 单位河北医科大学