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

From: The utility of the new generation of humanized mice to study HIV-1 infection: transmission, prevention, pathogenesis, and treatment

Mouse Model/HIV-1 strain Finding Reference
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]