Brain cell reservoirs of latent virus in presymptomatic HIV-infected individuals

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Katherine A Thompson1, Catherine L Cherry, Jeanne E Bell

  • 1Pathology Research Laboratory, Anatomical Pathology Unit, The Alfred Hospital, Department of Medicine, Monash University, Melbourne, Australia.

The American Journal of Pathology
|August 30, 2011
PubMed

Insights

Latent HIV-1 DNA exists in brain cells, including perivascular macrophages, microglia, and astrocytes, before HIV encephalitis develops. Macrophage trafficking of latent virus into the brain increases with immune suppression.

Area of Science:

  • Neuroscience
  • Immunology
  • Virology

Background:

  • Human Immunodeficiency Virus type 1 (HIV-1) establishes latent reservoirs in various tissues, including the brain.
  • The presence and distribution of these latent reservoirs in specific brain cell types during the early, asymptomatic stages of infection are not fully understood.
  • Understanding early viral reservoirs is crucial for developing effective eradication strategies.

Purpose of the Study:

  • To investigate the presence and cellular localization of latent HIV-1 DNA in the brain during the presymptomatic stage of infection.
  • To determine if specific brain cell populations harbor HIV-1 before the onset of pathological HIV encephalitis.
  • To explore the relationship between peripheral immune status and viral load in brain cells.

Main Methods:

  • Laser microdissection was used to isolate pure populations of perivascular macrophages, parenchymal microglia, and astrocytes from the brain tissue of five untreated individuals in the presymptomatic stage of HIV-1 infection.
  • Polymerase Chain Reaction (PCR) was employed to detect HIV-1 DNA within these isolated cell populations.
  • Peripheral blood CD4 counts were analyzed to assess the correlation with the presence of HIV-1 DNA in brain cells.

Main Results:

  • HIV-1 DNA was detected in all three isolated brain cell populations: perivascular macrophages, microglia, and astrocytes.
  • Detection of HIV-1 DNA was most consistent in perivascular macrophages.
  • No evidence of productive HIV-1 infection was observed in these cells.
  • A significant inverse correlation was found between the percentage of PCR reactions detecting HIV-1 DNA in perivascular macrophages and peripheral blood CD4 counts.

Conclusions:

  • Latent HIV-1 reservoirs exist in key brain cell types, including perivascular macrophages, microglia, and astrocytes, prior to the development of pathological HIV encephalitis.
  • Perivascular macrophages appear to be a primary site for latent HIV-1 in the brain during early infection.
  • Increased immunosuppression, indicated by lower CD4 counts, correlates with increased trafficking of latent HIV-1 by perivascular macrophages into the brain.

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