title: Is the central nervous system a reservoir of HIV-1?
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: aCentre for Biomedical Research, Burnet Institute bDepartment of Infectious Diseases, Monash University, Melbourne, Victoria cSouth Australian Health and Medical Research Institute, Adelaide, South Australia dDepartment of Microbiology and Immunology, University of Melbourne, Parkville eDepartment of Microbiology, Monash University, Clayton fDepartment of Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: Lachlan R
authors.initials: LR
authors.lastname: Gray
authors.forename: Michael
authors.initials: M
authors.lastname: Roche
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Flynn
authors.forename: Steve L
authors.initials: SL
authors.lastname: Wesselingh
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gorry
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Churchill
mesh_terms: D002490:Central Nervous System / Q000166:cytology / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009928:Organ Specificity; D019562:Viral Load; D017735:Virus Latency