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
Sanjay Swaminathan1-4#, Hongyan Sui1#, Joseph W Adelsberger1, Qian Chen1, Michael Sneller5, Stephen A Migueles5, Shyamasundaran Kottilil5, Alexander Ober5, Sara Jones6, Catherine A Rehm5, H Clifford Lane5 and Tomozumi Imamichi1*
- *Corresponding Author:
- Tomozumi Imamichi
Laboratory of Human Retrovirology
Building 550, Room 126, Leidos Biomedical Research Inc.
Frederick National Laboratory for Cancer Research
1050 Boyles St. Frederick, MD, USA, 21702
E-mail: [email protected]
Received Date: April 22, 2014; Accepted Date: May 26, 2014; Published Date: June 10, 2014
Citation: Swaminathan S, Sui H, Adelsberger JW, Chen Q, Sneller M, et al. (2014) 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. J AIDS Clin Res 5:315. doi:10.4172/2155-6113.1000315
Copyright: © 2014 Swaminathan S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objectives: After DNA or RNA virus infection, cytosolic foreign DNA or RNA derived from the infecting viruses is recognized by intracellular pathogen recognition receptors (PRRs) and induces activation of the innate immune system. Transfection of DNA has been used as an experimental model for DNA virus-mediated innate responses. We have previously reported that DNA transfection preferentially induces Type-III IFN (IFN-λ1) rather than Type-I IFN (IFN-β). In this study, we compared the DNA-mediated immune response between healthy controls and HIV-1 infected patients with undetectable viral loads and assessed potential innate immune responses in these patients.
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.
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.