Collot Marianne, Rouard Caroline, Brunet Christel, Agut Henri, Boutolleau David, Burrel Sonia
Centre Hospitalier et Universitaire de Nantes, Service de Virologie, Nantes, France; EA4271 « Immunovirology and Genetic Polymorphism », Université de Nantes, France.
AP-HP, Hôpital Universitaire Antoine Béclère, Service de Microbiologie, Clamart, France; EA4043 - Unité Bactéries Pathogènes et Santé UFR de Pharmacie-Université Paris-Sud, France.
Antiviral Res. 2016 Apr;128:1-6. doi: 10.1016/j.antiviral.2016.01.015. Epub 2016 Jan 28.
The emergence of herpes simplex virus (HSV) resistance to current antiviral drugs, that all target the viral DNA polymerase, constitutes a major obstacle to antiviral treatment effectiveness of HSV infections, especially in immunocompromised patients. A novel and promising class of inhibitors of the HSV UL5/UL52 helicase-primase (HP) complex has been reported to hinder viral replication with a high potency. In this study, we describe the low natural polymorphism (interstrain identity >99.1% at both nucleotide and amino acid levels) of HSV HP complex subunits pUL5 and pUL52 among 64 HSV (32 HSV-1 and 32 HSV-2) clinical isolates, and we show that the HSV resistance profile to the first-line antiviral drug acyclovir (ACV) does not impact on the natural polymorphism of HSV HP complex. Genotypic tools and polymorphism data concerning HSV HP complex provided herein will be useful to detect drug resistance mutations in a relevant time frame when HP inhibitors (HPIs), i.e., amenamevir and pritelivir, will be available in medical practice.
单纯疱疹病毒（HSV）对目前所有靶向病毒DNA聚合酶的抗病毒药物产生耐药性，这成为HSV感染抗病毒治疗有效性的主要障碍，尤其是在免疫功能低下的患者中。据报道，一类新型且有前景的HSV UL5/UL52解旋酶-引物酶（HP）复合物抑制剂能够高效地阻碍病毒复制。在本研究中，我们描述了64株HSV（32株HSV-1和32株HSV-2）临床分离株中HSV HP复合物亚基pUL5和pUL52的低自然多态性（核苷酸和氨基酸水平的株间同一性均>99.1%），并且我们表明HSV对一线抗病毒药物阿昔洛韦（ACV）的耐药谱并不影响HSV HP复合物的自然多态性。本文提供的有关HSV HP复合物的基因分型工具和多态性数据，将有助于在HP抑制剂（HPIs），即阿昔美韦和普瑞替韦，应用于医学实践的相关时间框架内检测耐药突变。
