Table 2 Mechanisms of HIV-1 pathogenesis in the new generation of humanized mice

RAG-hu mice; R5 tropic JR-CSF and dual-tropic R3A

CD4⁺FoxP3⁺ T regulatory cells are preferentially infected and depleted in spleen and lymph nodes; depletion occurs via apoptosis.

[61]

hNOG mice; R5 tropic JR-CSF or X4 tropic NL4-3

X4 tropic virus depletes both naïve and memory T cells, while R5 tropic virus selectively depletes effector memory T cells (CD45RO⁺CD45RA^-).

[72]

BLT mice; R5 tropic JR-CSF

R5 tropic virus depletes CD4⁺ effector memory T cells (CD45RA^-CD27^-) in small intestines

[77]

RAG-hu mice; R5 tropic YU-2

R5 tropic virus leads to translocation of LPS to the plasma, resulting in CD8 T cell activation, lower CD4 T cell ratios, and higher viral loads.

[51]

hNOG mice; R5 tropic ADA

Human macrophages, microglia, and dendritic cells are engrafted in the meninges and perivascular spaces in the hNOG brain. p24+ cells can be detected in the brain following intraperitoneal infection. Human immune cells infiltrate regions of viral replication in the brain, and CD8 T cell depletion leads to meningitis and encephalitis.

[75]

hNOG mice;R5 tropic ADA

HIV-1 infection leads to structural changes in brain architecture, leading to loss of neuronal integrity.

[76]

RAG-hu mice; dual-tropic R3A

Plasmacytoid dendritic cells (pDC) are productively infected and activated during early HIV infection, leading to CD4 T cell activation and apoptosis. pDC levels were stable, but function was impaired in the spleen and bone marrow.

[63]

BLT mice; NL4-3 backbone with LAI env gene

Virus with a single amino acid substitution in env (V38E) has similar viral load to virus with wild-type env, but is attenuated for CD4 T cell depletion due to a defect in caspase-dependent bystander apoptosis.

[80]