Table 1 Transgenic Rodent Models
From: Summary of presentations at the NIH/NIAID New Humanized Rodent Models 2007 Workshop
| Â | Dr. Goldstein | Dr. Keppler | Dr. Littman |
|---|---|---|---|
Characteristics of Humanized Rodent Models | Â | Â | Â |
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 | Â | Â | Â |
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infecting HIV | R5- HIV-JR-CSF | R5 HIV-1 (YU-2 and V3 loop recombinant NL4-3) for CD4/CCR5-tg; NL4-3 for CD4/CXCR4-tg (unpublished) | R5 HIV strains (CCR5 Tg mice) and X4 strains (CXCR4 Tg mice) |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 | Â | Â | Not examined due to lack of replication in vivo |
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 | Â | Â | Â |
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 | Â | Â | Not yet examined due to lack of replication |
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 |