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HIV reservoirs: what, where and how to target them

Nature Reviews Microbiology volume 14, pages 55–60 (2016)Cite this article

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Abstract

One of the main challenges in the fight against HIV infection is to develop strategies that are able to eliminate the persistent viral reservoir that harbours integrated, replication-competent provirus within host cellular DNA. This reservoir is resistant to antiretroviral therapy (ART) and to clearance by the immune system of the host; viruses originating from this reservoir lead to rebound viraemia once treatment is stopped, giving rise to new rounds of infection. Several studies have focused on elucidating the cells and tissues that harbour persistent virus, the true size of the reservoir and how best to target it, but these topics are the subject of ongoing debate. In this Viewpoint article, several experts in the field discuss the constitution of the viral reservoir, how best to measure it and the best ways to target this source of persistent infection.

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References

  1. Soriano-Sarabia, N. et al. Peripheral Vγ9Vδ2 T cells are a novel reservoir of latent HIV infection. PLoS Pathog. 11, e1005201 (2015).

    Article  Google Scholar 

  2. Churchill, M. J. et al. Use of laser capture microdissection to detect integrated HIV-1 DNA in macrophages and astrocytes from autopsy brain tissues. J. Neurovirol. 12, 146–152 (2006).

    Article  Google Scholar 

  3. Johnson, T. P. et al. Induction of IL-17 and nonclassical T-cell activation by HIV-Tat protein. Proc. Natl Acad. Sci. USA 110, 13588–13593 (2013).

    Article  CAS  Google Scholar 

  4. Canestri, A. et al. Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin. Infect. Dis. 50, 773–778 (2010).

    Article  Google Scholar 

  5. Dahl, V. et al. An example of genetically distinct HIV type 1 variants in cerebrospinal fluid and plasma during suppressive therapy. J. Infect. Dis. 209, 1618–1622 (2014).

    Article  Google Scholar 

  6. Peluso, M. J. et al. Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well controlled plasma viral load. AIDS 26, 1765–1774 (2012).

    Article  CAS  Google Scholar 

  7. Crooks, A. M. et al. Precise quantitation of the latent HIV-1 reservoir: implications for eradication strategies. J. Infect. Dis. 212, 1361–1365 (2015).

    Article  CAS  Google Scholar 

  8. Churchill, M. J. et al. Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia. Ann. Neurol. 66, 253–258 (2009).

    Article  Google Scholar 

  9. Glass, J. D., Fedor, H., Wesselingh, S. L., McArthur, J. C. Immunocytochemical quantitation of human immunodeficiency virus in the brain: correlations with dementia. Ann. Neurol. 38, 755–762 (1995).

    Article  CAS  Google Scholar 

  10. Gray, L. R. et al. CNS-specific regulatory elements in brain-derived HIV-1 strains affect responses to latency-reversing agents with implications for cure strategies. Mol. Psychiatry http://dx.doi.org/10.1038/mp.2015.111, (2015).

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Authors and Affiliations

  1. Melissa J. Churchill is at the Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria 3004, Australia.,

    Melissa J. Churchill

  2. Steven G. Deeks is at the Department of Medicine, University of California, San Francisco, California 94110, USA.,

    Steven G. Deeks

  3. and the Department of Medicine, David M. Margolis is at the University of North Carolina (UNC) HIV Cure Center, Institute of Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.,

    David M. Margolis

  4. Robert F. Siliciano is at the Department of Medicine and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.,

    Robert F. Siliciano

  5. the Department of Biochemistry and Biophysics, Ronald Swanstrom is at the Lineberger Comprehensive Cancer Center, and the University of North Carolina (UNC) Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.,

    Ronald Swanstrom

Authors
  1. Melissa J. Churchill
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  2. Steven G. Deeks
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  3. David M. Margolis
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  4. Robert F. Siliciano
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  5. Ronald Swanstrom
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Corresponding authors

Correspondence to Melissa J. Churchill, Steven G. Deeks, David M. Margolis, Robert F. Siliciano or Ronald Swanstrom.

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The authors declare no competing financial interests.

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Churchill, M., Deeks, S., Margolis, D. et al. HIV reservoirs: what, where and how to target them. Nat Rev Microbiol 14, 55–60 (2016). https://doi.org/10.1038/nrmicro.2015.5

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