Distribution of HIV genomic DNA in brains of AIDS patients
L E Bockstahler1, T Werner, H Festl
1Molecular Biology Branch, DLS, OST, CDRH, Food and Drug Administration, Rockville, MD, USA.
Background:
Data concerning the distribution of HIV in the brains of AIDS patients at different stages of viral infection might contribute towards: (1) understanding the route(s) of HIV entry into the brain and virus dissemination within the brain and (2) establishing a possible correlation between the extent of CNS damage and the distribution of virus in AIDS brains.
Objective:
To determine the distribution of HIV-1 genomic DNA within the brains of three deceased AIDS patients by polymerase chain reaction (PCR).
Study Design:
The brains of three deceased AIDS patients were examined. Two brains had limited neuropathologic findings (brains I and II), and one brain (brain III) showed primary HIV-specific neuropathologic damage. Tissues were taken from different locations within each brain, and high molecular weight DNA isolated from the tissues was assessed for HIV-1 genomic DNA by PCR.
Results:
HIV-1 genomic DNA was found in all three brains, but the amount was low: order of magnitude of 1 viral genome per 1,000 cells. Multiple PCR analyses of DNA from brain I showed that the viral genomic DNA in this brain was non-uniformly distributed; only samples taken from the brainstem were clearly positive for HIV-1. HIV-1 genomic DNA in brain II was found in portions of the lower and upper hemispheres. All but one of the brain III samples were clearly positive for HIV-1, and they had been taken from locations spread throughout this brain.
Conclusions:
Our results suggest that in early or latent stages of HIV-infection of the brain, viral genomic DNA is localized at restricted regions. At later stages this DNA is distributed more uniformly throughout the brain. Our data are compatible with the concept of rare infection events followed by viral spreading within brain tissues.
