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SIV Latency in Macrophages in the CNS

Part of the Current Topics in Microbiology and Immunology book series (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.

Keywords

  • Monocyte-derived Macrophages (MDMs)
  • Quantitative Viral Outgrowth Assay (QVOA)
  • Latent Reservoir
  • Viral Rebound
  • Latency-reversing Agents (LRA)

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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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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Correspondence to Janice E. Clements .

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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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