Co-Expression of miRNA Targeting the Expression of PERK, but Not PKR, Enhances Cellular Immunity from an HIV-1 Env DNA Vaccine
- Author(s)
- Wheatley, AK; Kramski, M; Alexander, MR; Toe, JG; Center, RJ; Purcell, DFJ;
- Details
- Publication Year 2011-03-25,Volume 6,Issue #3,Page e0018225
- Journal Title
- PLOS ONE
- Publication Type
- Journal Article
- Abstract
- Small non-coding micro-RNAs (miRNA) are important post-transcriptional regulators of mammalian gene expression that can be used to direct the knockdown of expression from targeted genes. We examined whether DNA vaccine vectors co-expressing miRNA with HIV-1 envelope (Env) antigens could influence the magnitude or quality of the immune responses to Env in mice. Human miR-155 and flanking regions from the non-protein encoding gene mirhg155 were introduced into an artificial intron within an expression vector for HIV-1 Env gp140. Using the miR-155-expressing intron as a scaffold, we developed novel vectors for miRNA-mediated targeting of the cellular antiviral proteins PKR and PERK, which significantly down-modulated target gene expression and led to increased Env expression in vitro. Finally, vaccinating BALB/c mice with a DNA vaccine vector delivering miRNA targeting PERK, but not PKR, was able to augment the generation of Env-specific T-cell immunity. This study provides proof-of-concept evidence that miRNA effectors incorporated into vaccine constructs can positively influence vaccine immunogenicity. Further testing of vaccine-encoded miRNA will determine if such strategies can enhance protective efficacy from vaccines against HIV-1 for eventual human use.
- Publisher
- PUBLIC LIBRARY SCIENCE
- Keywords
- PROTEIN-KINASE PKR; ENDOPLASMIC-RETICULUM-STRESS; DOUBLE-STRANDED-RNA; INITIATION-FACTOR 2; CD4 T-CELLS; IMMUNODEFICIENCY-VIRUS; MAMMALIAN-CELLS; BINDING-PROTEIN; MEDIATED-IMMUNITY; ENVELOPE PROTEIN
- Research Division(s)
- Infection And Immunity
- Publisher's Version
- https://doi.org/10.1371/journal.pone.0018225
- Open Access at Publisher's Site
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064671/- Terms of Use/Rights Notice
- Copyright Wheatley 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.
Creation Date: 2011-03-25 12:00:00