Antiviral function and efficacy of polyvalent immunoglobulin products against CMV isolates in different human cell lines
Antiviral function and efficacy of polyvalent immunoglobulin products against CMV isolates in different human cell lines
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DOI：
10.1007/s00430-012-0229-2
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发表时间：
2012-08-01
影响因子：
5.4
通讯作者：
Hofmann, J.
中科院分区：
文献类型：
--
作者：
Frenzel, K.;Ganepola, S.;Hofmann, J.
人类巨细胞病毒(CMV)的原发感染和再激活仍然是免疫功能低下患者的主要问题，经常导致危及生命的CMV疾病。静脉注射多价(超)免疫球蛋白(IVIG)可用于CMV感染的治疗和预防。然而，到目前为止，关于IVIG产品在体外抗病毒感染的有效性和作用机制的数据有限。在本研究中，使用CMV感染患者的分离物以及实验室分离株AD169和TB40，研究了IVIG在体外对CMV感染的影响。对五种不同的商业IVIG产品在不同的人类细胞系中进行了定性和定量的比较，研究了它们(1)中和无细胞病毒的能力，(2)抑制细胞间传播和细胞相关传播的能力，以及(3)影响CMV mRNA水平的能力。所有受试IVIG在上皮细胞和内皮细胞培养中均表现出较高的中和活性(50%抑制量；0.1 mg/ml)。然而，在用人胚胎肺成纤维细胞(HELF)进行的中和试验中，可以证明这两种产品之间的质量差异。IVIG产品在抑制CMV感染的HELF单层内细胞间传播的能力上也有显着差异，显示出61%至100%的抑制率。中和无细胞病毒的能力和抑制细胞间传播的能力之间没有相关性。IVIG孵育对CMV即刻早期和晚期信使核糖核酸的量有影响，表现为与IVIG孵育后感染的上皮细胞CMV信使核糖核酸显著降低，且呈剂量依赖关系。这项研究提示了多价IVIG的不同抗病毒功能，并证实了它们在体外抑制CMV感染的潜力，因此使用的IVIG产品之间存在显著差异。
Primary infection and reactivation of human cytomegalovirus (CMV) remain a major problem in immunocompromised patients, frequently resulting in a life threatening CMV disease. Intravenous polyvalent (hyper)-immunoglobulins (IVIG) can be administered for therapy and prophylaxis of CMV infections. However, only limited data about the efficacy and mechanism of action of IVIG products against viral infections in vitro are available so far. In this study, the effect of IVIG on CMV infection in vitro was investigated using isolates from CMV-infected patients as well as the laboratory strains AD169 and TB40. A qualitative and quantitative comparison of five different commercially available IVIG products in different human cell lines was performed concerning their ability (1) to neutralize cell-free virus, (2) to inhibit cell-to-cell spread and cell-associated transmission and (3) to influence CMV mRNA levels. All IVIG tested exhibited a high neutralization activity in epithelial and endothelial cell cultures (50% inhibition dose < 0.1 mg/ml). However, qualitative differences between the products could be demonstrated in neutralization tests using human embryonal lung fibroblasts (HELF). The IVIG products also significantly differed in their ability to inhibit cell-to-cell spread within an CMV-infected HELF monolayer displaying inhibition rates that varied between 61 and 100%. No correlation between the ability to neutralize cell-free virus and to inhibit cell-to-cell spread could be observed. The incubation with IVIG influenced the amount of CMV immediate early and late mRNA, as indicated by a significant reduction in CMV mRNA in infected epithelial cells after incubation with IVIG in a dose-dependent manner. This study suggests different antiviral functions of polyvalent IVIG and confirms their potential to inhibit a CMV infection in vitro, with profound differences between the hereby used IVIG products.