TY - JOUR
T1 - The dual role of dendritic cells in the immune response to human immunodeficiency virus type 1 infection
AU - Hogue, Ian B.
AU - Bajaria, Seema H.
AU - Fallert, Beth A.
AU - Qin, Shulin
AU - Reinhart, Todd A.
AU - Kirschner, Denise E.
PY - 2008
Y1 - 2008
N2 - 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 theser 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 quantilatively-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.
AB - 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 theser 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 quantilatively-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.
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U2 - 10.1099/vir.0.83600-0
DO - 10.1099/vir.0.83600-0
M3 - Article
C2 - 18753232
AN - SCOPUS:52649090615
SN - 0022-1317
VL - 89
SP - 2228
EP - 2239
JO - Journal of General Virology
JF - Journal of General Virology
IS - 9
ER -