Encyclopedia of AIDS

Living Edition
| Editors: Thomas J. Hope, Douglas Richman, Mario Stevenson

HIV Reservoirs in the Central Nervous System

  • Lauren Tompkins
  • Elena Dukhovlinova
  • Ronald Swanstrom
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9610-6_428-1


The central nervous system (CNS) is a unique anatomical compartment that is shielded from the rest of the body by the blood-brain barrier (BBB). Exchange of substances between the CNS and the blood is controlled and limited by the BBB. Human immunodeficiency virus (HIV) enters the CNS early after viral transmission and, in some cases, replicates independently of that in the blood. Viral replication in the CNS could be supported in multiple cell types including CD4+ T cells, macrophages, microglia, and potentially astrocytes or other cells lacking CD4 receptor expression. Following productive infection of permissive cells, it is plausible that viral species persist in the CNS in the form of a reservoir, or dormant state of infection that is capable of reactivation and production of new viral particles. Analyzing such a reservoir in the context of the CNS is challenging, given the fact that brain tissue can only be sampled at death. Yet, studies using cerebrospinal fluid (CSF)...

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  1. Archin NM, et al. Eradicating HIV-1 infection: seeking to clear a persistent pathogen. Nat Rev Microbiol. 2014;12(11):750–64.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Arrildt KT, et al. Phenotypic correlates of HIV-1 macrophage tropism. J Virol. 2015;89(22):11294–311.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Blankson JN, Persaud D, Siliciano RF. The challenge of viral reservoirs in HIV-1 infection. Annu Rev Med. 2002;53:557–93.CrossRefPubMedGoogle Scholar
  4. Burdo TH, et al. Increased monocyte turnover from bone marrow correlates with severity of SIV encephalitis and CD163 levels in plasma. PLoS Pathog. 2010;6(e1000842).Google Scholar
  5. Engelhardt B, Ransohoff RM. Capture, crawl, cross: the T cell code to breach the blood–brain barriers. Trends Immunol. 2012;33(12):579–89.CrossRefPubMedGoogle Scholar
  6. Ho YC, et al. Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell. 2013;155(3):540–51.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Joseph SB, et al. Quantification of entry phenotypes of macrophage-tropic HIV-1 across a wide range of CD4 densities. J Virol. 2014a;88(4):1858–69.Google Scholar
  8. Joseph SB, et al. HIV-1 target cells in the CNS. J Neurovirol. 2014b;21(3):276–89.Google Scholar
  9. Louveau A, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337–41.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Maldarelli F, et al. HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells. Science. 2014;345(6193):179–83.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Matsuda K, et al. Laser capture microdissection assessment of virus compartmentalization in the central nervous systems of macaques infected with neurovirulent simian immunodeficiency virus. J Virol. 2013;87(16):8896–908.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Monteiro de Almeida S, et al. Dynamics of monocyte chemoattractant protein type one (MCP-1) and HIV viral load in human cerebrospinal fluid and plasma. J Neuroimmunol. 2005;169(1–2):144–52.CrossRefPubMedGoogle Scholar
  13. Obermeier B, Daneman R, Ransohoff RM. Development, maintenance and disruption of the blood–brain barrier. Nat Med. 2013;19(12):1584–96.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Price RW, et al. Evolving character of chronic central nervous system HIV infection. Semin Neurol. 2014;34(1):7–13.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Ransohoff RM, Engelhardt B. The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol. 2012;12(9):623–35.CrossRefPubMedGoogle Scholar
  16. Siliciano RF, Greene WC. HIV latency. Cold Spring Harb Perspect Med. 2011;1(1):a007096.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Spector R, et al. A balanced view of choroid plexus structure and function: focus on adult humans. Exp Neurol. 2015;267:78–86.CrossRefPubMedGoogle Scholar
  18. Spudich SS, et al. Cerebrospinal fluid HIV infection and pleocytosis: relation to systemic infection and antiretroviral treatment. BMC Infect Dis. 2005;5:98.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Sturdevant CB, et al. Compartmentalized replication of R5 T cell-tropic HIV-1 in the central nervous system early in the course of infection. PLoS Pathog. 2015;11(3):e1004720.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Wakim LM, Woodward-Davis A, Bevan MJ. Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence. Proc Natl Acad Sci U S A. 2010;107(42):17872–9.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Watanabe R, et al. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells. Sci Transl Med. 2015;7(279):279ra39.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Yilmaz A, et al. Treatment intensification has no effect on the HIV-1 central nervous system infection in patients on suppressive antiretroviral therapy. J Acquir Immune Defic Syndr. 2010;55(5):590–6.CrossRefPubMedGoogle Scholar
  23. Zayyad Z, Spudich S. Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND). Curr HIV/AIDS Rep. 2015;12(1):16–24.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Zhuang K, et al. Emergence of CD4 independence envelopes and astrocyte infection in R5 simian-human immunodeficiency virus model of encephalitis. J Virol. 2014;88(15):8407–20.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Lauren Tompkins
  • Elena Dukhovlinova
  • Ronald Swanstrom
    • 1
  1. 1.The University of North CarolinaLineberger Cancer CenterChapel HillUSA