Characteristics of Humanized Rodent Models |
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Strain |
C.B-17 scid/scid (Taconic) |
NOD-SCID IL2r gamma -/- |
NOD/SCID |
# mice/donor |
50–60 mice/donor |
CD34+ cell isolation yields 1 × 106 cells/donor sufficient for engrafting 20- to 25 mice |
25 |
Source of human cells |
Human fetal liver and thymus (20–24 g.w.) |
Umbilical cord blood; mobilized hematopoeitic stem cells |
Fetal liver/thymus |
Method of isolation |
not applicable |
Magnetic bead enrichment |
Magnetic beads |
Pre-transplant treatment-mice |
None |
100 cGy for newborns; 325 cGy for adults; Intravenous injection |
325 rads |
Pre-transplant treatment-cells |
None |
None |
None |
Time frame from construction to experimental use |
18 weeks |
12 weeks |
8–12 weeks |
Location of human hematopoiesis |
Thy/Liv organ |
Bone marrow |
Bone marrow |
Location of human Thymopoiesis |
Thy/Liv organ |
Mouse thymus |
Human thymic tissue |
Reproducibility of engraftment (% mice engrafted) |
90–100% with >80% CD4+CD8+ |
>90% of newborn and adult mice are engrafted in the bone marrow, spleen and thymus |
>95% |
Identity of specific human leukocytes present |
Immature and mature T cells, B cells, macrophages, plasmacytoid DCs |
B cells, T cells, conventional and plasmacytoid DCs, macrophages, monocytes, RBCs, platelets |
T and B cells, DCs, monocytes/macrophages, NK, NKT and Tregs |
Populated tissues |
Human Thy/Liv organ |
Bone marrow, thymus, spleen, lymph nodes, intestine, blood |
GALT, Female and male reproductive tract, lung, bone marrow, lymph nodes, thymus, spleen, liver, peripheral blood. |
Characteristics of HIV Infection of Humanized Rodent Models |
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HIV-specific immune response |
None reported |
Work in progress |
Yes, human IgG |
Tropism/clade of infecting HIV |
X4, R5, dual/mixed; clade B |
Not tested |
R5 and X4 |
Target cells infected |
Intrathymic progenitors (CD3-CD4+CD8-), immature and mature thymocytes, macrophages |
Not tested |
CD4 T cells, monocytes/macrophages, DC |
Level of plasma HIV viremia |
None to highly variable |
Not tested |
Variable depending on stain of virus and tropism |
Duration of the infection |
5 weeks until severe depletion for X4 and dual/mixed; >6 months for R5 |
Not tested |
Variable depending on stain of virus and tropism |
Replication kinetics |
Peaks at 3 weeks post infection (wpi) (X4 and dual/mixed), 6 wpi (R5) |
Not tested |
Isolate dependent |
In vivo generation of ART resistance |
Not observed for NL4-3 and 3TC (no RT M184V) |
Not tested |
Not done |
Treatment of HIV Infection Using Humanized Rodent Models |
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ART to block transmission |
Not feasible |
Yes |
Not tested |
Microbicide to block transmission |
Not feasible |
Yes |
Not tested |
ART to control replication |
Yes, 4 classes of licensed ARVs so far. |
Yes |
Not tested |
Emergence of resistance to ART |
Not observed for NL4-3 and 3TC (no RT M184V) |
Not done |
Not tested |
Elimination of HIV reservoirs |
Not performed |
Not done |
Not tested |
HSC gene therapy to protect progeny cells |
Not performed |
yes |
Not tested |
CD4 T cell gene therapy to protect cells |
Not performed |
Not done |
Not tested |
Immune-based Therapy of HIV Infection Using Humanized Rodent Models |
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|
|
Preventive HIV vaccines |
Not feasible |
Yes |
Not tested |
Treatment HIV vaccines |
Not feasible |
Not done |
Not tested |
Adoptive Anti-HIV Ig therapy |
Feasible, but not performed |
Not done |
Not tested |
Adoptive Anti-HIV CTL therapy |
Feasible, but not performed |
Not done |
Not tested |
Immunoadjuvent therapy |
Not feasible |
Not done |
Not tested |
Investigation of HIV Pathogenesis |
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|
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Contribution of HIV genes to pathogenesis |
Nef, Env (coreceptor usage), protease |
Yes |
Not tested |
HIV-mediated CD4-depletion-lymphoid |
Thy/Liv organ |
Yes |
Not tested |
HIV-mediated CD4-depletion-mucosal |
Not applicable |
Yes |
Not tested |
Effects of co-factors on replication |
Not determined |
Yes |
Not tested |
Effects of co-infection e.g. mTb on replication |
Not determined |
Yes |
Not tested |
End organ dysfunction |
Thy/Liv organ undergoes severe thymocyte depletion |
Yes |
Not tested |