From: Summary of presentations at the NIH/NIAID New Humanized Rodent Models 2007 Workshop
 | Dr. Akkina | Drs. Speck and Luban | Dr. Su |
---|---|---|---|
Characteristics of Humanized Rodent Models | Â | Â | Â |
Strain | Balb/c-Rag2-/-γ c-/- | Balb/c-Rag2-/-γ c-/- | Balb/c-Rag2-/-γ c-/- |
# mice/donor | 40/donor | CD34+ cell isolation yields 1–2 × 106 cells/donor sufficient for 5–10 mice (1 litter) | 20–50/donor |
Source of human cells | Fetal liver | Cord blood | Fetal liver |
Method of isolation | Magnetic bead enrichment for CD34+ cells | Magnetic bead enrichment for CD34+ cells | CD34+ MACS kit |
Pre-transplant treatment-mice | Irradiation 350 rads; intrahepatic injection into newborns | Irradiation 200 rads given twice 4 h apart; intrahepatic injection into newborns | Irradiation 400 rad; intrahepatic injection into newborns |
Pre-transplant treatment-cells | SCF, IL-3, IL-6 | None | None or retroviral transduction |
Time frame from construction to experimental use | 12 weeks | 12–16 weeks | >12 weeks |
Location of human hematopoiesis | Bone marrow | Not investigated | BM, Spleen, LN |
Location of human Thymopoiesis | Mouse thymus | Not investigated | Mouse thymus |
Reproducibility of engraftment (% mice engrafted) | >95% | More than 90% of mice show human cells in periphery; about 50% of mice have levels >10% huCD45+ cells | >95% with >20% human CD45+ cells in blood |
Identity of specific human leukocytes present | T and B cells, DCs, monocytes/macrophages and some granulocytes | B and T cells, monocytes, DCs | All human leukocytes |
Populated tissues | Bone marrow, lymph nodes, thymus, spleen, liver, intestines, lungs | Thymus, spleen, blood, MLN, BM, liver; to some extent: gut | BM/thymus/spleen/LN (no significant Peyer's patches found) |
Characteristics of HIV Infection of Humanized Rodent Models | Â | Â | Â |
HIV-specific immune response | Not detected | Some minor B cell response (1/25 animals tested); no T cell response detected | Low gag-specific responses/no IgG detected |
Tropism/clade of infecting HIV | R5, X4, dual-tropic | YU-2 and NL4-3 | R5-X4-dual or R5/clade B |
Target cells infected | CD4 T cells | CD3+ cells and only occasionally non T cells such as CD68+ macrophages | CD4 T and DC |
Level of plasma HIV viremia | ~107 copies RNA/ml | Up to 2 × 106 copies/ml | 105-106 copies/ml |
Duration of the infection | at least 14 months | Up to 190 days; longest period followed | >22 weeks |
Replication kinetics | Peak viremia at about 6 weeks followed by maintenance of viremia | HIV RNA levels peak 2–6 wpi, thereafter viremia mostly stabilizes at lower levels. | HIV RNA levels peaks at 2–3 (dual tropic) or 4–6 wpi (R5-tropic) |
In vivo generation of ART resistance | Not done | Not tested | Not known |
Treatment of HIV Infection Using Humanized Rodent Models | Â | Â | Â |
ART to block transmission | Not done | Not done | Not done |
Microbicide to block transmission | Not done | Not done | Not done |
ART to control replication | Not done | Not done | Yes. |
Emergence of resistance to ART | Not done | Not done | Not done |
Elimination of HIV reservoirs | Not done | Not done | Not done |
HSC gene therapy to protect progeny cells | yes | Not done | Not done |
CD4 T cell gene therapy to protect cells | Not done | Not done | Not done |
Immune-based Therapy of HIV Infection Using Humanized Rodent Models | Â | Not done | Â |
Preventive HIV vaccines | Not done | Not done | Not done |
Treatment HIV vaccines | Not done | Not done | Not done |
Adoptive Anti-HIV Ig therapy | Not done | Not done | Not done |
Adoptive Anti-HIV CTL therapy | Not done | Not done | Not done |
Immunoadjuvent therapy | Not done | Not done | Not done |
Investigation of HIV Pathogenesis | Â | Â | Â |
Contribution of HIV genes to pathogenesis | yes | Not done | Env/Nef |
HIV-mediated CD4-depletion-lymphoid | yes | yes | Yes |
HIV-mediated CD4-depletion-mucosal | Not done | Not done | mesenteric LN, yes |
Effects of co-factors on replication | Not done | Not done | Not done |
Effects of co-infection e.g. mTb on replication | Not done | Not done | Not done |
End organ dysfunction | Not done | Not done | Not done |