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SIV Latency in Macrophages in the CNS

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Book cover HIV-1 Latency

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 417))

Abstract

Lentiviruses infect myeloid cells, leading to acute infection followed by persistent/latent infections not cleared by the host immune system. HIV and SIV are lentiviruses that infect CD4+ lymphocytes in addition to myeloid cells in blood and tissues. HIV infection of myeloid cells in brain, lung, and heart causes tissue-specific diseases that are mostly observed during severe immunosuppression, when the number of circulating CD4+ T cells declines to exceeding low levels. Antiretroviral therapy (ART) controls viral replication but does not successfully eliminate latent virus, which leads to viral rebound once ART is interrupted. HIV latency in CD4+ lymphocytes is the main focus of research and concern when HIV eradication efforts are considered. However, myeloid cells in tissues are long-lived and have not been routinely examined as a potential reservoir. Based on a quantitative viral outgrowth assay (QVOA) designed to evaluate latently infected CD4+ lymphocytes, a similar protocol was developed for the assessment of latently infected myeloid cells in blood and tissues. Using an SIV ART model, it was demonstrated that myeloid cells in blood and brain harbor latent SIV that can be reactivated and produce infectious virus in vitro, demonstrating that myeloid cells have the potential to be an additional latent reservoir of HIV that should be considered during HIV eradication strategies.

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Acknowledgements

These studies were funded by NIH awards R01NS089482, R01NS077869, P40OD0131117, R01NS055651, R56AI118753, R01AI127142, P01MH070306, P01AI131306, 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

    Lucio Gama, Celina Abreu, Erin N. Shirk, Suzanne E. Queen, Sarah E. Beck, Kelly A. Metcalf Pate, Brandon T. Bullock, M. Christine Zink, Joseph L. Mankowski & Janice E. Clements

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

    Joseph L. Mankowski & Janice E. Clements

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

    Joseph L. Mankowski & Janice E. Clements

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  1. Lucio Gama
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Correspondence to Janice E. Clements .

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  1. School of Medicine, Emory University, Atlanta, GA, USA

    Guido Silvestri

  2. The Brigham and Women’s Hospital and the Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA

    Mathias Lichterfeld

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Gama, L. et al. (2018). SIV Latency in Macrophages in the CNS. In: Silvestri, G., Lichterfeld, M. (eds) HIV-1 Latency. Current Topics in Microbiology and Immunology, vol 417. Springer, Cham. https://doi.org/10.1007/82_2018_89

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