HIV-1 infection and HAART can lead to cytopenias affecting blood cell formation and immune responses in infected patients. The PI will utilize the SCID mouse transplanted with human fetal thymus and liver tissues (SCID-hu Thy/Liv) to study the mechanisms of HIV-1 and HAART induced multilineage hematopoietic inhibition and testing cytokines and drug therapies. The PI will focus this research investigation on the hematopoietic cytokine, thrombopoietin (Tpo) and its receptor (c-mpl) since they are important effectors of multilineage hematopoiesis. The c-mpl is primarily associated with differentiation of CD34+ cells into megakaryocytes.
The Specific aims of the proposal are as following: (1) to determine hematopoietic revival effects of CD34+c-mpl+ versus CD34+c-mpl- cells obtained from HIV-1 infected SCID-hu mouse in the presence or absence of HAART, following re-engraftment and reconstitution of these CD34+ cell subsets in the Thy/Liv implants of SCID-hu recipients, (2) to determine the effects of cytokine treatment and HAART on the c-mpl expression and hematopoietic revival effects of CD34+c-mpl+ versus CD34+c-mpl- cells, and (3) to determine if engraftment of CD34+ cells transduced with a lentiviral vector carrying human c-mpl gene into the SCID-hu Thy/Liv implants and cytokine treatment will contribute to multilineage hematopoiesis in HIV-1 infection.
|Yuan, Jinyun; Devarajan, Asokan; Moya-Castro, Rosita et al. (2010) Putative innate immunity of antiatherogenic paraoxanase-2 via STAT5 signal transduction in HIV-1 infection of hematopoietic TF-1 cells and in SCID-hu mice. J Stem Cells 5:43-8|
|Zhang, Menghua; Dias, Peter; Minev, Boris et al. (2010) Induction characterization and targeting of human hematopoietic cancer stem cells. J Stem Cells 5:1-7|
|Sundell, I Birgitta; Halder, Ramesh; Zhang, Menghua et al. (2010) Sulfatide administration leads to inhibition of HIV-1 replication and enhanced hematopoeisis. J Stem Cells 5:33-42|
|Zhang, Menghua; Evans, Stella; Yuan, Jinyun et al. (2010) HIV-1 determinants of thrombocytopenia at the stage of CD34+ progenitor cell differentiation in vivo lie in the viral envelope gp120 V3 loop region. Virology 401:131-6|
|Zhang, Menghua; Poh, Tuang Yeow; Louache, Fawzia et al. (2009) Rescue of multi-lineage hematopoiesis during HIV-1 infection by human c-mpl gene transfer and reconstitution of CD34+ progenitor cells in vivo. J Stem Cells 4:161-77|
|Yunis, Edmond J; Romero, Viviana; Diaz-Giffero, Felipe et al. (2007) Natural Killer Cell Receptor NKG2A/HLA-E Interaction Dependent Differential Thymopoiesis of Hematopoietic Progenitor Cells Influences the Outcome of HIV Infection. J Stem Cells 2:237-248|
|Sundell, I Birgitta; Koka, Prasad S (2006) Chimeric SCID-hu Model as a Human Hematopoietic Stem Cell Host That Recapitulates the Effects of HIV-1 on Bone Marrow Progenitors in Infected Patients. J Stem Cells 1:283-300|
|Yunis, Edmond J; Zuniga, Joaquin; Koka, Prasad S et al. (2006) Stem Cells in Aging: Influence of Ontogenic, Genetic and Environmental Factors. J Stem Cells 1:125-147|
|Sundell, I Birgitta; Koka, Prasad S (2006) Thrombocytopenia in HIV infection: impairment of platelet formation and loss correlates with increased c-Mpl and ligand thrombopoietin expression. Curr HIV Res 4:107-16|
|Brooks, David G; Cohen, Michael D; Jamieson, Beth D et al. (2005) Rapid size dependent deletion of foreign gene sequences inserted into attenuated HIV-1 upon infection in vivo: implications for vaccine development. Curr HIV Res 3:377-92|
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