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HCV replication in PBMC and its influence on interferon therapy

机译:PBMC中的HCV复制及其对干扰素治疗的影响

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AIM: To study hepatic virus C (HCV) RNA and HCV protein expression in peripheral blood mononuclear cells (PBMCs) of patients with HCV infection, and explore the relationship between the HCV RNA in the PBMCs and response to interferon (IFN) therapy. METHODS: Type-specific primers were designed and RT-nested PCR was used to detect the plus- and minus- strands of HCV RNA in PBMCs of 54 patients with HCV infection; Indirect immunofluorescence assay was applied to identify HCVNS5 protein expression in PBMCs; 6 month-, 3 MU-IFN regiment was administrated to observe the responses to IFN in 35 chronic hepatitis C patients with different HCV RNA status in PBMCs. RESULTS: HCV plus strand RNA was found in 10 of 19 (52.6%) acute hepatitis C patients and 22 of 35 (62.9%) chronic hepatitis C patients. HCV minus strand RNA was detected in 14 of 35 (40.0%) chronic hepatitis C patients, but only one patient (5.3%) with acute HCV infection was found to be minus HCV RNA positive. Though no HCV NS5 protein expression was found in the examined 10 cases of acute HCV infection, it was positive in 17 of 20 (85.0%) chronic hepatitis C patients by indirect immunofluoresence assay. There are significant differences of positive rate of the minus-strand and HCVNS5 protein between acute and chronic hepatitis C groups(u=2.07, P<0.05 and u=4.43, P<0.01 respectively). The patients with minus-strand HCV RNA showed a significantly lower 6-month sustained response (SR-6) to IFN compared to those without minus-strand HCVRNA in PBMCs (biologically 14.3% vs 42.8%, x~2=4.12, P<0.05 and virologically 7.1% vs 23.9%, x~2=4.24, P<0.05). CONCLUSION: HCV is capable of infecting and replicating in PBMCs, and HCVNS5 protein was expressed in PBMCs. The patients with minus strand HCV RNA in PBMCs showed a significantly lower 6-month sustained response to IFN, suggesting that minus-strand HCV RNA in PBMCs may be one of the factors influencing response to IFN therapy.
机译:目的:研究丙型肝炎病毒感染患者外周血单个核细胞(PBMC)中丙型肝炎病毒(HCV)RNA和HCV蛋白的表达,探讨PBMC中HCV RNA与干扰素(IFN)治疗反应之间的关系。方法:设计54型HCV感染患者PBMCs中的特异性引物,采用RT-nested PCR检测HCV RNA的正负链。应用间接免疫荧光法鉴定PBMC中HCVNS5蛋白的表达。给予6个月,3 MU-IFN方案以观察PBMC中35例具有不同HCV RNA状态的慢性丙型肝炎患者对IFN的反应。结果:19例急性丙型肝炎患者中有10例(52.6%)和35例慢性丙型肝炎患者中有22例发现HCV加链RNA。在35例慢性丙型肝炎患者中,有14例(40.0%)检测到HCV负链RNA,但仅一名急性HCV感染的患者(5.3%)被发现为HCV负链阳性。尽管在检查的10例急性HCV感染病例中未发现HCV NS5蛋白表达,但通过间接免疫荧光测定法在20例慢性丙型肝炎患者中有17例(85.0%)呈阳性。急性和慢性丙型肝炎组的负链和HCVNS5蛋白阳性率有显着差异(分别为u = 2.07,P <0.05和u = 4.43,P <0.01)。 PBMC中具有负链HCV RNA的患者对IFN的6个月持续应答(SR-6)明显低于无负链HCVRNA的患者(生物学上分别为14.3%vs 42.8%,x〜2 = 4.12,P < 0.05和病毒学上的7.1%和23.9%,x〜2 = 4.24,P <0.05)。结论:HCV能够在PBMC中感染和复制,并且HCVNS5蛋白在PBMC中表达。 PBMC中有负链HCV RNA的患者对IFN的6个月持续缓解显着降低,这表明PBMC中的负链HCV RNA可能是影响对IFN治疗反应的因素之一。

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