A modified SCID mouse model of HIV infection with utility for testing anti-HIV therapies.
Using human tumor cells we have developed a mouse model of active HIV infection that may be used for testing antiviral agents, although it does not reflect the pathogenesis of human infection. Irradiated SCID/NOD mice are injected with a tumor of human CD4+ lymphoma cells susceptible to infection and at a separate site, tumor cells persistently infected with either primary or T cell line-adapted strains of HIV. The spread of infection from the infected to the susceptible tumor is monitored as plasma p24 and the presence of HIV-infected cells in the spleen. We have used this model to examine the relative efficacy of neutralizing anti-HIV antibodies to halt the spread of infection. We have found that the tetrameric CD4-antibody fusion protein, CD4-IgG2, is highly effective compared to an anti-V3 loop antibody. This animal model, while not replicating the human disease, allows for the simultaneous testing of efficacy, toxicity, and pharmacokinetics of potential new antiviral therapies. The model can easily be powered to enable comparisons between different therapeutic agents and dosing regimens.
Pincus
Seth H
SH
Department of Microbiology, Montana State University, Bozeman, MT 59717, USA. spincus@chnola-research.org
Fang
Hua
H
Wilkinson
Royce A
RA
Olson
William C
WC
Marcotte
Tamera K
TK
D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000627:therapeutic use*; D016860:CD4 Immunoadhesins / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013154:Spleen / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014407:Tumor Cells, Cultured
D019380:Anti-HIV Agents; D000914:Antibodies, Viral; D016860:CD4 Immunoadhesins