Comparisons of HIV-1 viral sequences in brain, choroid plexus and spleen: potential role of choroid plexus in the pathogenesis of HIV encephalitis.

Possible mechanisms of HIV transmission to the brain include direct viral infection of cerebral endothelium and hematogeneous dissemination of viral-infected lymphocytes and monocytes. Cerebrospinal fluid dissemination from a primary infection of choroid plexus (CPx) is an alternative mechanism supported by recent studies in our laboratory. We showed that HIV-infected asymptomatic patients as well as AIDS patients have HIV infection of the CPx; the cell types so infected included stromal monocytes and dendritic cells. To further explore the potential role of CPx in the pathogenesis of HIV encephalitis, we analyzed HIV sequences from brain, CPx, and spleen of four AIDS patients by extracting DNA from paraffin sections and amplifying the V3 region of the HIV env gene by PCR. Several different clones from each tissue were characterized. We found that viruses from the brain and spleen grouped into two distinct clusters, while viruses of the CPx contained viral strains that were a mixture of those found in the brain or spleen. Net charge analysis of the V3 tip region showed that the brain viral sequences had fewer positive charges than blood viral sequences. Our results support the hypothesis that CPx may be one of the sites where HIV-1 gains access to the brain from the blood and therefore contains viruses that are of both genotypes.