HIV-1 Treated Patients with Undetectable Viral Loads have Lower Levels of Innate Immune Responses via Cytosolic DNA Sensing Systems Compared with Healthy Uninfected Controls

与未感染病毒的健康对照组相比,接受 HIV-1 治疗且病毒载量无法检测的患者通过细胞质 DNA 传感系统产生的先天免疫反应水平较低

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作者:Sanjay Swaminathan, Hongyan Sui, Joseph W Adelsberger, Qian Chen, Michael Sneller, Stephen A Migueles, Shyamasundaran Kottilil, Alexander Ober, Sara Jones, Catherine A Rehm, H Clifford Lane, Tomozumi Imamichi

Conclusion

HIV-1 treated patients with undetectable viral loads have lower levels of innate immune responses via cytosolic DNA sensing systems. This may be caused by persistent immune activation.

Methods

The study consisted of 50 HIV-1 negative healthy donors, 46 patients on combination antiretroviral therapy with HIV-1 viral loads <50 copies/ml and 7 long term non-progressors (LTNPs). PBMCs were isolated from whole blood using Ficoll-Paque. DNA transfection was performed using Lipofectamine 2000. After 22 hours incubation, total cellular RNA was extracted and real time RT-PCR was performed to determine gene expression level of IFN-λ1, IFN-β and RANTES. Gene induction was compared by fold change.

Results

Baseline levels of endogenous gene expression of IFN-λ1, IFN-β and RANTES in HIV-1 patients were higher than in controls. Following DNA transfection, both HIV infected patients and healthy controls induced gene induction, however, the induction in HIV-1 patients was at a significantly lower level compared to uninfected controls.

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