title: Accumulation of nuclear and mitochondrial DNA damage in the frontal cortex cells of patients with HIV-associated neurocognitive disorders.
abstract: Oxidative stress has been suggested to play a key role in the neuropathogenesis of HIV infection. HIV proteins (gp120, Tat) and proinflammatory cytokines can trigger the production of reactive oxygen species (ROS), resulting in DNA and RNA lesions. Among all the lesions induced by ROS, one of the most abundant lesions in DNA and RNA is 8-hydroxydeoxyguanosine (8-oxoG). Here, we studied accumulated DNA oxidative damage induced by ROS in the central nervous system (CNS) in tissue from neuro-AIDS patients. The frontal cortex of autopsy tissue from HIV-1 infected patients was adopted for analysis for HIV-1 subtype, nuclear and mitochondrial DNA lesions by immunofluorescence staining, qPCR and sequencing of PCR cloning. This study provides evidence that HIV infection in the CNS leads to nuclear and mitochondrial genomic DNA damage in the brain. High level of nuclear and mtDNA 8-oxoG damage were identified in the cortex autopsy tissue of HAND patients. Increased accumulation of mtDNA mutations and depletion occurs in brain tissue in a subset of HAND cases, and is significantly different from that observed in control cases. These findings suggest that higher level of ROS in the CNS of HAND patients would contribute to the HIV induced neuro-inflammation and apoptosis of neuronal and glial cells.
authors.affiliation: Department of Medicine, Beijing You An Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Meixia
authors.initials: M
authors.lastname: Wang
authors.forename: Hongjun
authors.initials: H
authors.lastname: Li
authors.forename: Honghai
authors.initials: H
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.forename: Feili
authors.initials: F
authors.lastname: Wei
authors.forename: Daojie
authors.initials: D
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.forename: Dexi
authors.initials: D
authors.lastname: Chen
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000235:genetics* / Q000473:pathology; D002648:Child; D003072:Cognition Disorders / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004249:DNA Damage / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology*; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D020014:K562 Cells; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000235:genetics; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial