Damage and repair of DNA in HIV encephalitis

Neuronal damage and dementia are common sequelae of HIV encephalitis. The m echanism by which HIV infection of CNS macrophages results in neuronal dama ge is not known. We examined the brains from 15 AIDS autopsies (8 with HIV encephalitis and 7 without) and 4 non-infected control autopsies for the pr esence of DNA strand breaks, for associated changes in the expression of th e DNA repair enzymes KU80 and Poly (ADP-ribose) polymerase (PARP), and for accumulation of amyloid precursor protein (APP).,Abundant DNA damage was ob served with terminal transferase-mediated dUTP nick end-labeling (TUNEL), h owever, there was no morphologic evidence of significant neuroglial apoptos is. The DNA repair enzyme KU80 was immunocytochemically detectable in neuro nal and glial cells in autopsy brains from patients with and without HIV en cephalitis; however, in cases with HIV encephalitis the staining was more p rominent than in the infected or non-infected controls without encephalitis . There was no difference in KU80 immunostaining in oligodendroglia from au topsies with and without encephalitis. Immunostaining for PARP was more int ense in gray and white matter of cases with HIV encephalitis. No clear spat ial relationship existed between expression of DNA repair enzymes and the s patial proximity of microglial nodules or HIV-infected macrophages. The cyt oplasm of cortical and subcortical neurons immunostained for APP. Stronger cortical neuronal APP staining was observed in cases without HIV encephalit is. Staining of deep gray matter neurons was similar, irrespective of the p resence or absence of encephalitis. While foci of intense APP staining were noted in white matter not related to HIV infection, they were associated w ith foci of opportunistic infections (e.g. due to CMV or PML). We conclude that damaged DNA and altered patterns of expression of DNA repair proteins and APP are common findings in the brains of AIDS patients at autopsy, but do not have a spatial relationship to HN-infected macrophages.