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骨髓移植后发生脑炎的多重耐药型巨细胞病毒 UL54 突变株的分隔现象。

Compartmentalization of a Multidrug-Resistant Cytomegalovirus UL54 Mutant in a Stem Cell Transplant Recipient with Encephalitis.

机构信息

Centre de recherche en infectiologie, CHU de Québec-Université Laval.

Laboratory of Virology and Infectious Diseases Division, Geneva, Switzerland.

出版信息

J Infect Dis. 2019 Sep 13;220(8):1302-1306. doi: 10.1093/infdis/jiz298.

Abstract

We report a case of cytomegalovirus encephalitis in a hematopoietic stem cell transplant recipient. A previously uncharacterized V787E mutation in UL54 was identified in cerebrospinal fluid but not plasma specimens. For the V787E recombinant virus, the half maximal effective concentrations for ganciclovir, foscarnet, and cidofovir were 8.6-, 3.4- and 2.9-fold higher than for wild-type virus, and the replicative capacity was lower. The introduction of a bulkier and negatively charged glutamate residue at position 787 could destabilize the finger domain of UL54 DNA polymerase. Viral genotyping of cerebrospinal fluid is warranted in subjects with cytomegalovirus encephalitis, owing to the low penetration of antivirals in this compartment.

摘要

我们报告了一例造血干细胞移植受者的巨细胞病毒性脑炎。在脑脊液而不是血浆标本中发现了 UL54 中以前未表征的 V787E 突变。对于 V787E 重组病毒,更昔洛韦、膦甲酸和西多福韦的半数最大有效浓度比野生型病毒分别高 8.6、3.4 和 2.9 倍,复制能力更低。在位置 787 处引入更大和带负电荷的谷氨酸残基可能会使 UL54 DNA 聚合酶的指状结构域失稳。由于抗病毒药物在该部位的穿透性低,因此应在患有巨细胞病毒性脑炎的患者中对脑脊液进行病毒基因分型。

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