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Transgenic Rodent Models |
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| Dr. Goldstein |
Dr. Keppler |
Dr. Littman |
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| Characteristics of Humanized Rodent Models |
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| Strain |
Full-length LTR-regulated HIV provirus and CD-promoter regulated human cyclin T1 expressed as transgenes in mice |
Human CD4, CCR5 and cycin T 1 expressed as transgenes in Sprague-Dawley rats |
Human CD4, CCR5 and cycin T 1 expressed as transgenes in mice |
| # mice/donor |
NA |
NA |
NA |
| Source of human cells |
NA |
NA |
NA |
| Method of isolation |
NA |
NA |
NA |
| Pre-transplant treatment-mice |
NA |
NA |
NA |
| Pre-transplant treatment-cells |
NA |
NA |
NA |
| Time frame from construction to experimental use |
immediately |
Immediately |
immediately |
| Location of human hematopoiesis |
NA |
NA |
NA |
| Location of human Thymopoiesis |
NA |
NA |
NA |
| Reproducibility of engraftment (% mice engrafted) |
NA |
NA |
NA |
| Identity of specific human leukocytes present |
NA |
NA |
NA |
| Populated tissues |
HIV provirus and infectious HIV produced by CD4 lymphocytes, macrophages, DC and microglia in all organs analyzed |
Human transgenes expressed in rat CD4 lymphocytes, macrophages and microglia in all tissues analyzed |
Mouse CD4 T cells and monocyte lineages, including macrophages, dendritic cells, and microglia |
| Characteristics of HIV Infection of Humanized Rodent Models |
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| HIV-specific immune response |
None |
Robust seroconversion, cellular responses not analyzed. |
not examined |
| Tropism/clade of infecting HIV |
R5- HIV-JR-CSF |
R5 HIV-1 (YU-2 and V3 loop recombinant NL4-3) for CD4/CCR5-tg; NL4-3 for CD4/CXCR4-tg (unpublished) |
R5 HIV strains (CCR5 Tg mice) and X4 strains (CXCR4 Tg mice) |
| Target cells infected |
All cells |
CD4 T-cells, macrophages |
CD4+ T cells, macrophages, microglia |
| Level of plasma HIV viremia |
102~105 copies RNA/ml |
2 × 102 RNA/ml (transient) |
not observed |
| Duration of the infection |
Life of the mouse |
Low level viremia up to 7 weeks, low levels of 2-LTR circles at 6 months |
not observed |
| Replication kinetics |
Inducible by cellular activation |
NA |
NA |
| In vivo generation of ART resistance |
NA |
NA |
NA |
| Treatment of HIV Infection Using Humanized Rodent Models |
Not examined due to lack of replication in vivo |
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| ART to block transmission |
NA |
Pre-EP and post-EP for efavirenz, enfuvirtide |
NA |
| Microbicide to block transmission |
NA |
NA |
NA |
| ART to control replication |
NA |
NA |
NA |
| Emergence of resistance to ART |
NA |
NA |
NA |
| Elimination of HIV reservoirs |
NA |
NA |
NA |
| HSC gene therapy to protect progeny cells |
NA |
NA |
NA |
| CD4 T cell gene therapy to protect cells |
NA |
NA |
NA |
| Immune-based Therapy of HIV Infection Using Humanized Rodent Models |
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| Preventive HIV vaccines |
NA |
In progress (humoral immunity) |
NA |
| Treatment HIV vaccines |
NA |
NA |
NA |
| Adoptive Anti-HIV Ig therapy |
NA |
NA |
NA |
| Adoptive Anti-HIV CTL therapy |
NA |
NA |
NA |
| Immunoadjuvent therapy |
NA |
NA |
NA |
| Investigation of HIV Pathogenesis |
Not yet examined due to lack of replication |
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| Contribution of HIV genes to pathogenesis |
yes |
NA |
NA |
| HIV-mediated CD4-depletion-lymphoid |
yes |
NA |
NA |
| HIV-mediated CD4-depletion-mucosal |
yes |
NA |
NA |
| Effects of co-factors on replication |
yes |
CD4, CCR5, CXCR4, CyclinT1 |
CD4, CCR5, CXCR4, Cyclin T1, DC-SIGN |
| Effects of co-infection e.g. mTb on replication |
yes |
NA |
NA |
| End organ dysfunction |
yes |
NA |
NA |
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NA = not applicable | |||
Goldstein AIDS Research and Therapy 2008 5:3 doi:10.1186/1742-6405-5-3 |
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