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Animal Models

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Osteopontin Is an Integral Mediator of Cardiac Interstitial Fibrosis in Models of Human Immunodeficiency Virus Infection

Robinson et al., The Journal of Infectious Diseases. 2023.

https://www.doi.org/10.1093/infdis/jiad149

HIV infection is associated with increased risk of cardiovascular disease. Plasma osteopontin (Opn) is correlated with cardiac pathology, but more work is needed to understand the underlying mechanisms driving cardiac fibrosis. Researchers explored this topic using mouse embryonic fibroblasts, male macaques, and humanized mice of both sexes. They reported the accumulation of Opn in the heart with simian immunodeficiency virus infection. Systemic inhibition of Opn can prevent HIV-associated interstitial fibrosis in the left ventricle. These findings suggest that Opn could be a potential target for adjunctive therapies to reduce cardiac fibrosis in people with HIV. Supported by ORIP (P51OD011104), NIAID, NHLBI, NIMH, and NINDS.

A Participant-Derived Xenograft Model of HIV Enables Long-Term Evaluation of Autologous Immunotherapies

McCann et al., Journal of Experimental Medicine. 2021.

https://doi.org/10.1084/jem.20201908

HIV-specific CD8+ T cells partially control viral replication but rarely provide lasting protection due to immune escape. Investigators showed that engrafting NSG mice with memory CD4+ T cells from HIV+ donors enables evaluation of autologous T cell responses while avoiding graft-versus-host disease. Treating HIV-infected mice with clinically relevant T cell products reduced viremia. In vivo activity was significantly enhanced when T cells were engineered with surface-conjugated nanogels carrying an Interleukin-15 superagonist but was ultimately limited by the pervasive selection of escape mutations, recapitulating human patterns. This “participant-derived xenograft” model provides a powerful tool for developing T cell-based therapies for HIV. Supported by ORIP (R01OD011095), NIAID, NIDA, NIMH, NINDS, and NCATS.