Laboratoire de Virologie, Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, France.
Service d'Hématologie Clinique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, France.
Antiviral Res. 2019 Aug;168:114-120. doi: 10.1016/j.antiviral.2019.05.012. Epub 2019 May 30.
Genotypic diagnosis of HSV drug resistance can be performed routinely in a clinically relevant time. Nevertheless, data about HSV mutations (polymorphism or resistance) is not exhaustive which hinders the interpretation of such tests. The UL23, UL30, and UL5 genes are of greatest interest as these encode, respectively, thymidine kinase, DNA polymerase, and helicase, which, if mutated may affect the effectiveness of acyclovir, foscarnet, cidofovir, and helicase-primase inhibitors. The present study aimed to extensively characterize UL23, UL30, and UL5 genes. A total of 239 clinical HSV1 recovered from patients admitted to the hematology departments of the Lyon teaching hospitals were included in this single-center retrospective study. Drug resistance was evaluated using the neutral red dye-uptake assay, and sequencing using the Sanger method. Additional information on HSV1 natural polymorphism and resistance is now available. Twenty-two amino acid substitutions related to polymorphism were described on UL23 (E43A, L50M, L68R, Q109K, A133V, A136N, S150L, D258N, S263L, P280S, N301S, A316S, M322L, I326V, D330A, D338H, Q342H, T344I, Q349R, V352L, R370W, E371D), and 6 amino acid substitutions on UL30 (G641R, G645D, E649G, G679D, R681L, I966M). Moreover, the UL23 substitution L242P was added to ACV resistance-related mutations. There were 12 substitutions on UL23 (A37S, V70M, S74L, H151N, P154S, P155Q, L159R, E225L, Y248H, Q270R, N303Y, M372I), and 8 on UL5 (L49I, L138V, S173L, A280T, A575V, V600A, A602T, D862N) that remain of unclear significance with regards to drug resistance. The mean (±standard deviation, SD) number of natural polymorphisms in UL23 was 2.53 (±2.55), in UL30 it was 0.83 (±1.02), and in UL5 it was 5.00 (±1.59) There was no association between HSV1 phenotype and the frequency of substitutions. The results reported herein provide valuable new information concerning HSV1 mutations that will assist the interpretation of genotypic assays.
单纯疱疹病毒耐药性的基因诊断可以在临床相关的时间内常规进行。然而，有关单纯疱疹病毒突变（多态性或耐药性）的数据并不详尽，这阻碍了此类检测结果的解释。UL23、UL30 和 UL5 基因最为重要，因为它们分别编码胸苷激酶、DNA 聚合酶和螺旋酶，如果发生突变，可能会影响阿昔洛韦、磷甲酸、西多福韦和螺旋酶-引物抑制剂的疗效。本研究旨在对 UL23、UL30 和 UL5 基因进行广泛的特征描述。这项单中心回顾性研究共纳入了 239 例从里昂教学医院血液科住院患者中分离出的单纯疱疹病毒 1 型。采用中性红染料摄取试验和 Sanger 测序法评估耐药性。现在有更多关于单纯疱疹病毒 1 型自然多态性和耐药性的信息。在 UL23 上描述了 22 个与多态性相关的氨基酸取代（E43A、L50M、L68R、Q109K、A133V、A136N、S150L、D258N、S263L、P280S、N301S、A316S、M322L、I326V、D330A、D338H、Q342H、T344I、Q349R、V352L、R370W、E371D），在 UL30 上有 6 个氨基酸取代（G641R、G645D、E649G、G679D、R681L、I966M）。此外，在与 ACV 耐药相关的突变中增加了 UL23 取代 L242P。UL23 上有 12 个取代（A37S、V70M、S74L、H151N、P154S、P155Q、L159R、E225L、Y248H、Q270R、N303Y、M372I），UL5 上有 8 个取代（L49I、L138V、S173L、A280T、A575V、V600A、A602T、D862N），它们与耐药性仍不清楚。UL23 的平均（±标准偏差，SD）自然多态性数量为 2.53（±2.55），UL30 为 0.83（±1.02），UL5 为 5.00（±1.59）。单纯疱疹病毒 1 表型与取代频率之间没有关联。本报告的结果提供了有关单纯疱疹病毒 1 突变的有价值的新信息，这将有助于解释基因分型检测结果。
