title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research (FNLCR), Frederick, MD 21702, USA ; Department of Clinical Immunology, Western Sydney Local Health District, Sydney, Australia ; Sydney Medical School, University of Sydney, Sydney, Australia ; School of Medicine, University of Western Sydney, Sydney, Australia.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research (FNLCR), Frederick, MD 21702, USA.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Sui
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research (FNLCR), Frederick, MD 21702, USA.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Adelsberger
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research (FNLCR), Frederick, MD 21702, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Sneller
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Migueles
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Shyamasundaran
authors.initials: S
authors.lastname: Kottilil
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ober
authors.affiliation: Clinical Research Program Directorate, Leidos Biomedical Research, Inc., FNLCR, Frederick, MD 21702, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Jones
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Rehm
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
authors.affiliation: Applied and Developmental Research Directorate, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research (FNLCR), Frederick, MD 21702, USA.
authors.forename: Tomozumi
authors.initials: T
authors.lastname: Imamichi
keywords: Cytosolic DNA sensors; DNA sensing; DNA virus; HIV-1; IFN-β; IFN-λ1; Innate immunity; RANTES