Table 1.
Summary of the current humanized mouse models for HIV-1 CNS pathology studies
| Model | Method of humanization | Human cell reconstitution of CNS | Characterization of CNS pathology | Characterization of behavior/learning | Evaluation of ART in the CNS |
|---|---|---|---|---|---|
| Direct brain injection mouse models | |||||
| SCID-HIVE | Injection of HIV-1 infected MDMs into the brain of SCID mice | Human macrophages present throughout brain | Encephalitis, astrogliosis, multinucleated giant cells, infiltration of murine mononuclear phagocytes, decreased MAP-2 expression | Impaired learning and memory |
Zidovudine/Lamivudine/Indinavir: decreased levels of MAP-2, TNF-alpha mRNA, viral load, and astrogliosis Atazanavir/Tenfovir/Emtricitabine: decreased inflammatory response |
| huPBL/HIVE | Injection of HIV-1 infected MDMs into basal ganglia of NOD/SCID mice previously injected with human peripheral blood lymphocytes | Human macrophages present throughout brain | Multinucleated giant cells and T cell infiltration into the brain | Not evaluated to date | Not evaluated to date |
| Systemic reconstitution mouse models | |||||
| huPBMC | Injection of human PBMCs into adult NOD/SCID mice | Human T cells present in meninges (but no macrophages), after LPS injection human macrophages migrate to the brain | After LPS administration astrocytosis, microglial nodules (nodules present with/without HIV), and upregulation of TRAIL are observed | Not evaluated to date | Not evaluated to date |
| huNSG/huNOG | Injection of human HSC into the liver of newborn NSG/NOG mice | Macrophage repopulation of the meninges/perivascular spaces | HIV infection led to an increase in the number of human cells in the brain; loss of neuronal integrity | Not evaluated to date | Not evaluated to date |
| huNOD/SCID | Tail-vein injection of human HSC into adult NOD/SCID mice | Human Alu sequences present in cerebral cortex, cerebellum, colliculus and olfactory bulbs suggesting the presence of human cells | not evaluated to date | ||
| BLT | Implantation of human thymus and liver under the kidney capsule followed by autologous HSC transplant into NSG mice | Not evaluated to date | |||