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HIV mediates a productive infection of the brain
C A Wiley1, C L Achim, C Christopherson
1Department of Pathology, University of Pittsburgh Medical Center, PA, USA.
Background:
Approximately one quarter of patients with AIDS develop severe cognitive deficits called HIV-associated dementia complex. There is some controversy regarding the importance of viral load and distribution in mediating this neurologic disease.
Objective:
Brain HIV proviral and RNA loads were compared to define the molecular nature of HIV infection of the brain.
Method:
Neuropathologic examination was performed on brains from 10 autopsies of patients with AIDS that had short post-mortem intervals and no evidence of opportunistic infection. Viral DNA and RNA were extracted and quantified from multiple brain regions. These findings were compared with triple-label immunofluorescence for viral and cell markers.
Results:
Brains with histopathologic evidence of HIV encephalitis contained abundant HIV RNA and DNA. Regions without productive HIV infection showed minimal proviral load. By immunocytochemistry, only brain macrophages/microglia double labeled for viral proteins.
Conclusions:
HIV mediates a productive infection of brain macrophages/microglia. There was no evidence supporting the hypothesis of substantial neuronal or macroglial infection, or evidence of substantial proviral burden prior to the development of productive infection.