The dual role of dendritic cells in the immune response to human immunodeficiency virus type 1 infection
dc.contributor.author | Hogue, Ian Barclay | |
dc.contributor.author | Bajaria, Seema H. | |
dc.contributor.author | Fallert, Beth A. | |
dc.contributor.author | Qin, Shulin | |
dc.contributor.author | Reinhart, Todd A. | |
dc.contributor.author | Kirschner, Denise E. | |
dc.date.accessioned | 2011-03-28T18:14:12Z | |
dc.date.accessioned | 2011-03-28T18:14:12Z | |
dc.date.available | 2011-03-28T18:14:12Z | en_US |
dc.date.issued | 2008-04-25 | |
dc.identifier.citation | Journal of General Virology (2008), 89, 2228–2239 <http://hdl.handle.net/2027.42/83355> | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/83355 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/pubmed?term=18753232 | |
dc.description.abstract | Many aspects of the complex interaction between human immunodeficiency virus type 1 (HIV-1) and the human immune system remain elusive. Our objective was to study these interactions, focusing on the specific roles of dendritic cells (DCs). DCs enhance HIV-1 infection processes as well as promote an antiviral immune response. We explored the implications of these dual roles. A mathematical model describing the dynamics of HIV-1, CD4+ and CD8+ T-cells, and DCs interacting in a human lymph node was analysed and is presented here. We have validated the behaviour of our model against non-human primate simian immunodeficiency virus experimental data and published human HIV-1 data. Our model qualitatively and quantitatively recapitulates clinical HIV-1 infection dynamics. We have performed sensitivity analyses on the model to determine which mechanisms strongly affect infection dynamics. Sensitivity analysis identifies system interactions that contribute to infection progression, including DC-related mechanisms. We have compared DC-dependent and -independent routes of CD4+ T-cell infection. The model predicted that simultaneous priming and infection of T cells by DCs drives early infection dynamics when activated T-helper cell numbers are low. Further, our model predicted that, while direct failure of DC function and an indirect failure due to loss of CD4+ T-helper cells are both significant contributors to infection dynamics, the former has a more significant impact on HIV-1 immunopathogenesis. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Society for General Microbiology | en_US |
dc.title | The dual role of dendritic cells in the immune response to human immunodeficiency virus type 1 infection | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Microbiology and Immunology | |
dc.subject.hlbtoplevel | Health Sciences | |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Microbiology and Immunology, Department of | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 18753232 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/83355/1/IBHogueEtAll.2008.vir83600.v2.pdf | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/83355/2/hogue-JGV2008-erratum.pdf | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/83355/3/jgv2008-suppl.pdf | |
dc.identifier.doi | 10.1099/vir.0.83600-0 | |
dc.identifier.source | Journal of General Virology | en_US |
dc.owningcollname | Microbiology and Immunology, Department of |
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