Is the central nervous system a reservoir of HIV-1?

Lachlan R. Gray, Michael Roche, Jacqueline K. Flynn, Steven Wesselingh, Paul R. Gorry, Melissa J. Churchill

Research output: Contribution to journalReview article

61 Citations (Scopus)

Abstract

Purpose of review To summarize the evidence in the literature that supports the central nervous system (CNS) as a viral reservoir for HIV-1 and to prioritize future research efforts. Recent findings HIV-1 DNA has been detected in brain tissue of patients with undetectable viral load or neurocognitive disorders, and is associated with long-lived cells such as astrocytes and microglia. In neurocognitively normal patients, HIV-1 can be found at high frequency in these cells (4% of astrocytes and 20% of macrophages). CNS cells have unique molecular mechanisms to suppress viral replication and induce latency, which include increased expression of dominant negative transcription factors and suppressive epigenetic factors. There is also evidence of continued inflammation in patients lacking a CNS viral load, suggesting the production and activity of viral neurotoxins (for example, Tat). Summary Together, these findings provide evidence that the CNS can potentially act as a viral reservoir of HIV-1. However, the majority of these studies were performed in historical cohorts (absence of combination antiretroviral therapy or presence of viral load), which do not reflect modern day patients (combination antiretroviral therapy-treated and undetectable viral load). Future studies will need to examine patient samples with these characteristics to conclusively determine whether the CNS represents a relevant and important viral reservoir.

LanguageEnglish
Pages552-558
Number of pages7
JournalCurrent Opinion in HIV and AIDS
Volume9
Issue number6
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Central nervous system
  • Cure
  • HIV-1
  • Latency
  • Reservoirs

ASJC Scopus subject areas

  • Immunology
  • Hematology
  • Oncology
  • Oncology(nursing)
  • Infectious Diseases
  • Virology

Cite this

Gray, L. R., Roche, M., Flynn, J. K., Wesselingh, S., Gorry, P. R., & Churchill, M. J. (2014). Is the central nervous system a reservoir of HIV-1? Current Opinion in HIV and AIDS, 9(6), 552-558. https://doi.org/10.1097/COH.0000000000000108