Restricted and selective tropism of a Venezuelan equine encephalitis virus-derived replicon vector for human dendritic cells.
Abstract: Dendritic cells (DCs) consist of heterogeneous phenotypic populations and have diverse immunostimulatory functions dependent on both lineage and functional phenotype, but as exceptionally potent antigen-presenting cells, they are targets for generating effective antigen-specific immune responses. A promising replicon particle vector derived from Venezuelan equine encephalitis virus (VEE) has been reported to transduce murine footpad DCs. However, the receptive DC subset, the degree of restriction for this tropism, and the extent of conservation between rodents and humans have not been well characterized. Using fresh peripheral blood DCs, mononuclear cells, monocyte-derived macrophages, and monocyte-derived DCs, our results demonstrate conservation of VEE replicon particle (VRP) tropism for DCs between humans and rodents. We observed that a subset of immature myeloid DCs is the target population, and that VRP-transduced immature DCs retain intact functional capacity, for example, the ability to resist the cytopathic effects of VRP transduction and the capacity to acquire the mature phenotype. These studies support the demonstration of selective VRP tropism for human DCs and provide further insight into the biology of the VRP vector, its parent virus, and human DCs.
Publication Date: 2007-04-12 PubMed ID: 17425424DOI: 10.1089/vim.2006.0090Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research study investigates the interaction of a specific virus-derived vector with human dendritic cells, in order to better understand potential applications for immune response stimulations.
Research Objective and Background
- The study aimed to understand the receptive subset of cells, the level of restriction for this affinity, and the conservation of this affinity across different species, specifically humans and rodents. All of these were poorly understood.
- The researchers have used a replicon particle vector, derived from the Venezuelan equine encephalitis virus (VEE).
- This vector has already shown promising results in transducing dendritic cells in mice.
- Dendritic cells (DCs) are notably potent antigen-presenting cells with different phenotypic populations and diverse immunostimulatory functions. Due to this, they are excellent targets for generating effective antigen-specific immune responses.
Methodology
- The research utilized fresh peripheral blood dendritic cells, mononuclear cells, monocyte-derived macrophages, and monocyte-derived dendritic cells to assess the interaction with the VEE derived vector.
Findings
- The results showed conservation of VEE replicon particle (VRP) tropism for dendritic cells across both humans and rodents.
- It was found that a subset of immature myeloid dendritic cells is the target population.
- Importantly, dendritic cells transduced with VRP retained their functional capacity, such as the ability to resist the cytopathic effects caused by VRP transduction and the ability to acquire a mature phenotype.
Implications
- These findings provide strong evidence of selective VRP tropism for human dendritic cells, which might have significant implications in the field of antigen-specific immune responses.
- This research further enhances our understanding of the biology of the VRP vector, its parent virus (VEE), and human dendritic cells.
Cite This Article
APA
Nishimoto KP, Laust AK, Wang K, Kamrud KI, Hubby B, Smith JF, Nelson EL.
(2007).
Restricted and selective tropism of a Venezuelan equine encephalitis virus-derived replicon vector for human dendritic cells.
Viral Immunol, 20(1), 88-104.
https://doi.org/10.1089/vim.2006.0090 Publication
Researcher Affiliations
- Molecular Biology and Biochemistry, School of Medicine, School of Biological Sciences, University of California, Irvine, Irvine, California 92697, USA.
MeSH Terms
- Dendritic Cells / physiology
- Dendritic Cells / virology
- Encephalitis Virus, Venezuelan Equine / genetics
- Encephalitis Virus, Venezuelan Equine / immunology
- Genetic Vectors / genetics
- Humans
- Replicon
- Transduction, Genetic
- Tropism
Grant Funding
- P30 CA062203 / NCI NIH HHS
- P41 EB015890 / NIBIB NIH HHS
Citations
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