Impact of Genetic Polymorphisms in Cytomegalovirus Glycoprotein B on Outcomes in Solid-Organ Transplant Recipients with Cytomegalovirus Disease
Impact of Genetic Polymorphisms in Cytomegalovirus Glycoprotein B on Outcomes in Solid-Organ Transplant Recipients with Cytomegalovirus Disease
复制标题
DOI：
10.1086/605633
复制
发表时间：
2009-10-15
影响因子：
11.8
通讯作者：
Humar, Atul
中科院分区：
文献类型：
--
作者：
Manuel, Oriol;Asberg, Anders;Humar, Atul
背景资料。目前尚不清楚巨细胞病毒(CMV)病患者体内病毒基因多态性是否影响体内治疗反应。CMV糖蛋白B(GB)基因的多态可以区分4种不同的基因类型(GB1-gB4)。我们评估了gB基因对巨细胞病毒病的临床和病毒学结果的影响。参加CMV病治疗多中心试验(Victor研究)的固体器官移植受者包括在这项研究中。在开始抗病毒治疗的第0天，用实时定量聚合酶链式反应进行CMV gB基因分型。在239例巨细胞病毒病患者中，GB1、GB2、GB3和GB4株的感染率分别为26%、10%、10%和5%，混合感染率为49%。供者血清阳性/受者血清阳性患者比供者血清阳性/受者血清阴性患者更有可能患有混合GB感染(40%对12%)。与单一基因感染相比，混合感染的中位基线病毒载量更高，病毒根除时间更长(分别为P=.005和P=.026)。在多变量模型中，在控制了基线病毒载量、基线CMV血清水平、更昔洛韦耐药性和抗病毒治疗后，混合GB感染是第21天前未能根除病毒的显著预测因素(混合与单一基因型；优势比2.66；95%可信区间1.31-5.38；P=0.007)。GB基因对CMV的病毒学和临床复发无影响。似乎没有特定的gB基因赋予特定的CMV毒力优势。然而，混合gB基因感染与较高的病毒载量和延迟的病毒清除有关。
Background. It is unknown whether specific viral polymorphisms affect in vivo therapeutic response in patients with cytomegalovirus (CMV) disease. Polymorphisms in the CMV glycoprotein B (gB) gene allow discrimination of 4 distinct genotypes (gB1-gB4). We assessed the influence of gB genotypes on the clinical and virologic outcome of CMV disease.Methods. Solid-organ transplant recipients enrolled in a multicenter trial of CMV disease treatment (VICTOR study) were included in this study. CMV gB genotyping was performed using quantitative real-time polymerase chain reaction at day 0 (start of antiviral therapy).Results. Among 239 patients with CMV disease, the prevalence of gB strain types was 26% for gB1, 10% for gB2, 10% for gB3, and 5% for gB4, whereas mixed infections were present in 49%. Donor-seropositive/recipientseropositive patients were more likely to have mixed gB infection than donor-seropositive/recipient-seronegative patients (40% vs. 12%;). Median baseline viral P < .001 loads were higher and time to viral eradication was longer (P = .005 and P = .026, respectively) for mixed infection versus infection with a single genotype. In a multivariate model, mixed gB infection was a significant predictor of failure to eradicate virus by day 21 (mixed vs single genotype; odds ratio, 2.66; 95% confidence interval, 1.31-5.38; P = .007) after controlling for baseline viral load, CMV serostatus at baseline, ganciclovir resistance, and antiviral treatment. No effect of gB genotype was seen on virologic or clinical CMV recurrence.Conclusions. No specific gB genotype appears to confer a specific CMV virulence advantage. However, mixed gB genotype infections are associated with higher viral loads and delayed viral clearance.