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急性和慢性HIV-1感染患者中JAK/STAT途径中干扰素λ相关基因和蛋白的动态变化

The dynamic changes of interferon lambdas related genes and proteins in JAK/STAT pathway in both acute and chronic HIV-1 infected patients.

作者信息

Zhao Guoxian, Liu Lifeng, Su Bin, Zhang Tong, Chen Peng, Li Wei, Wu Hao

机构信息

Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, 100069 China.

Beijing Key Laboratory for HIV/AIDS Research, Beijing, 100069 China.

出版信息

AIDS Res Ther. 2017 Jun 17;14(1):31. doi: 10.1186/s12981-017-0158-7.

Abstract

BACKGROUND

Host immune responses during acute HIV-1 infection can influence the viral setpoint, which is a predictor of disease progression. Interferon (IFN)-lambdas are newly classified type III interferons, which use JAK-STAT pathway. Currently, the dynamics of IFN-lambdas related genes and proteins expression in the signaling pathway have not been well elaborated, especially in acute HIV-1-infected patients.

OBJECTIVES

To evaluate the dynamic changes of IFN-lambdas related genes and proteins in JAK/STAT pathway in acute HIV-1-infected patients, and analyze their correlation with CD4 T cell counts and HIV-1 viral loads.

STUDY DESIGN

Real-time PCR and flow cytometry methods were used to evaluate the dynamic changes of IFN-lambdas related genes and proteins in JAK/STAT pathway in both acute and chronic HIV-1-infected patients.

RESULTS

The IFN-alpha receptors (R), IFN-gamma R, IFN-lambdas R and STAT1 mRNA and protein levels increased in acute HIV-1-infected patients (p < 0.01), in addition, Mx1 mRNA levels in acute HIV-1-infected patients are higher than those in HIV-negative subjects. IFN-lambdas R and IFN-alpha R mRNA levels are inversely correlated with CD4 T-cell counts, but are positively correlated with viral loads.

CONCLUSIONS

The dynamic changes of IFNs related genes in JAK-STAT pathway in acute HIV-1 infection will deepen our understanding of the roles of IFN-lambdas in HIV pathogenesis.

摘要

背景

急性HIV-1感染期间宿主免疫反应可影响病毒载量设定点,而病毒载量设定点是疾病进展的一个预测指标。干扰素(IFN)-λ是新分类的III型干扰素,其利用JAK-STAT信号通路。目前,信号通路中IFN-λ相关基因和蛋白表达的动态变化尚未得到充分阐述,尤其是在急性HIV-1感染患者中。

目的

评估急性HIV-1感染患者JAK/STAT信号通路中IFN-λ相关基因和蛋白的动态变化,并分析它们与CD4 T细胞计数和HIV-1病毒载量的相关性。

研究设计

采用实时PCR和流式细胞术方法评估急性和慢性HIV-1感染患者JAK/STAT信号通路中IFN-λ相关基因和蛋白的动态变化。

结果

急性HIV-1感染患者中,IFN-α受体(R)、IFN-γ R、IFN-λ R以及STAT1的mRNA和蛋白水平升高(p < 0.01),此外,急性HIV-1感染患者的Mx1 mRNA水平高于HIV阴性受试者。IFN-λ R和IFN-α R的mRNA水平与CD4 T细胞计数呈负相关,但与病毒载量呈正相关。

结论

急性HIV-1感染中JAK-STAT信号通路中IFN相关基因的动态变化将加深我们对IFN-λ在HIV发病机制中作用的理解。

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