Introduction

Cytomegalovirus (CMV) predisposes to several clinical complications and is a major cause of morbidity and mortality in immunocompromised patients, including patients with hematological malignancies (HM). The present study was carried out to determine the distribution of CMV glycoprotein B, N, and O (gB, gN, and gO) genotypes and their potential effect on its viral load and on clinical outcomes in a cohort of Tunisian non-hematopoietic stem cell transplant (HSCT) patients with HM undergoing chemotherapy.

Methods

CMV viral load was evaluated by real-time quantitative PCR. The gB, gN, and gO genotypes of the CMV strains were analyzed by multiplex nested PCR and sequencing.

Results

This prospective study involved 60 clinical isolates obtained from 60 non-HSCT patients with HM undergoing chemotherapy. Mixed CMV gB, gN, and gO genotypes were the predominant glycoprotein genotypes in 31%, 41.4%, and 46.4% of patients, respectively. Mixed gB genotypes were associated with higher initial levels of CMV load (p = 0.001), increased rate of fever (0.025), and co-infection with other herpesviruses (HHVs) (p = 0.024) more frequently than in single gB genotype. Mixed gN genotypes were more associated with severe lymphopenia (ALC < 500/µL) (p = 0.01) and increased risk of death (p = 0.042) than single gN genotype. Single gO2b genotype had also a more unfavorable outcome (p = 0.009) than the other single gO genotype. Mixed gO genotypes were associated with female gender (p = 0.015), acute leukemia disease (p = 0.036), initial high level of CMV viral load (at least 1000 copies/mL) (p = 0.029), skin rash (p = 0.01) more frequently than in single gO genotype. The gO1a/gN3b linkage was associated with an increased initial viral load (p = 0.012).

Conclusion

Infection with mixed CMV genotypes was common and multiple gB, gN, and gO genotypes were associated with clinical manifestation and higher viral load.

中文翻译：

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接受化疗的非移植性血液系统恶性肿瘤患者的巨细胞病毒糖蛋白多态性和病毒载量增加：一项前瞻性观察研究

介绍

巨细胞病毒 (CMV) 易引发多种临床并发症，是免疫功能低下患者（包括血液系统恶性肿瘤 (HM) 患者）发病率和死亡率的主要原因。本研究旨在确定 CMV 糖蛋白 B、N 和 O（gB、gN 和 gO）基因型的分布及其对突尼斯非造血干细胞队列中病毒载量和临床结果的潜在影响接受化疗的 HM 移植（HSCT）患者。

方法

通过实时定量 PCR 评估 CMV 病毒载量。通过多重嵌套 PCR 和测序分析 CMV 毒株的 gB、gN 和 gO 基因型。

结果

这项前瞻性研究涉及来自 60 名接受化疗的 HM 非 HSCT 患者的 60 种临床分离株。混合 CMV gB、gN 和 gO 基因型分别是 31%、41.4% 和 46.4% 的患者的主要糖蛋白基因型。与 单一 gB 基因型相比，混合 gB 基因型与更高的初始 CMV 负荷水平 ( p  = 0.001)、发热率增加 (0.025) 以及与其他疱疹病毒 (HHV) 合并感染 ( p = 0.024) 的频率更高。与 单一 gN 基因型相比，混合 gN 基因型与严重淋巴细胞减少 (ALC < 500/µL) ( p  = 0.01) 和死亡风险增加 ( p = 0.042) 相关性更高。单一的 gO2b 基因型也有更不利的结果（p = 0.009) 比其他单一的 gO 基因型。混合 gO 基因型与女性（p  = 0.015）、急性白血病（p  = 0.036）、初始高水平 CMV 病毒载量（至少 1000 拷贝/mL）（p  = 0.029）、皮疹（p  = 0.01）相关) 比单一 gO 基因型更频繁。gO1a/gN3b 连接与增加的初始病毒载量相关 ( p  = 0.012)。

结论

混合 CMV 基因型感染很常见，多种 gB、gN 和 gO 基因型与临床表现和更高的病毒载量相关。