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An SIV/macaque model targeted to study HIV-associated neurocognitive disorders

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Abstract

Simian immunodeficiency virus (SIV) infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HIV-associated neurocognitive disorders (HAND) for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high-translational value. Similar to observations in HIV-infected patients receiving antiretroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART. By developing quantitative viral outgrowth assays that measure both CD4+ T cells and macrophages harboring replication competent SIV as well as a highly sensitive mouse-based viral outgrowth assay, we have positioned the SIV/pigtailed macaque model to advance our understanding of latent cellular reservoirs, including potential CNS reservoirs, to promote HIV cure. In addition to contributing to our understanding of the pathogenesis of HAND, the SIV/pigtailed macaque model also provides an excellent opportunity to test innovative approaches to eliminate the latent HIV reservoir in the brain.

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Acknowledgements

These studies were funded by NIH awards R01NS089482, R01 NS077869, P40OD0131117, R01NS055651, R56AI118753, R01AI127142, P01MH070306, and the Johns Hopkins University Center for AIDS Research P30AI094189.

Anti-retroviral compounds for these studies were kindly donated by Gilead, ViiV Healthcare, Bristol-Meyers Squibb, Merck, Abbvie, Janssen, and Roche. These studies were supported by the excellent technical staff in the Retrovirus Lab at Johns Hopkins.

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Authors and Affiliations

  1. Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, 21205, USA

    Sarah E. Beck, Suzanne E. Queen, Kelly A. Metcalf Pate, Lisa M. Mangus, Celina M. Abreu, Lucio Gama, Kenneth W. Witwer, Robert J. Adams, M. Christine Zink, Janice E. Clements & Joseph L. Mankowski

  2. Department of Neurology, Johns Hopkins University, Baltimore, MD, 21205, USA

    Kenneth W. Witwer, Janice E. Clements & Joseph L. Mankowski

  3. Department of Pathology, Johns Hopkins University, Baltimore, MD, 21205, USA

    Janice E. Clements & Joseph L. Mankowski

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  1. Sarah E. Beck
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  2. Suzanne E. Queen
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  3. Kelly A. Metcalf Pate
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  4. Lisa M. Mangus
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  5. Celina M. Abreu
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  6. Lucio Gama
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  7. Kenneth W. Witwer
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  8. Robert J. Adams
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  9. M. Christine Zink
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  10. Janice E. Clements
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  11. Joseph L. Mankowski
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Correspondence to Joseph L. Mankowski.

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Beck, S.E., Queen, S.E., Metcalf Pate, K.A. et al. An SIV/macaque model targeted to study HIV-associated neurocognitive disorders. J. Neurovirol. 24, 204–212 (2018). https://doi.org/10.1007/s13365-017-0582-4

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