Increased human immunodeficiency virus (HIV) type 1 DNA content and quinolinic acid concentration in brain tissues from patients with HIV encephalopathy.
Levels of human immunodeficiency virus type 1 (HIV-1) DNA and quinolinic acid were examined in areas of the central nervous system (CNS) and lymphoid organs (LN) from 5 AIDS patients with no clinically apparent CNS compromise (group I), 7 with CNS opportunistic diseases (group II), and 8 with HIV encephalopathy (group III). The brains from patients with HIV encephalopathy not only contained higher levels of HIV-1 DNA (cerebrum, P < .01; cerebellum, P < .05) as assessed by quantitative polymerase chain reaction but also showed a higher rate of viral pol region mutations suggestive of zidovudine or didanosine resistance than brains from patients in group I or II (P < .01). CNS quinolinic acid concentrations were significantly higher in group II and III patients than in group I (P = .03), even though quinolinic acid levels in LN were comparable among the 3 groups. These data suggest that CNS inflammatory changes associated with HIV encephalopathy may be triggered by a local productive HIV-1 infection within the CNS.
Sei
S
S
Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Saito
K
K
Stewart
S K
SK
Crowley
J S
JS
Brouwers
P
P
Kleiner
D E
DE
Katz
D A
DA
Pizzo
P A
PA
Heyes
M P
MP
D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000473:pathology / Q000821:virology*; D017088:AIDS-Related Opportunistic Infections / Q000473:pathology / Q000821:virology; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001921:Brain / Q000821:virology*; D001923:Brain Chemistry; D002478:Cells, Cultured; D002531:Cerebellum / Q000821:virology; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis*; D016049:Didanosine / Q000627:therapeutic use; D015751:Genes, pol; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D008264:Macrophages / Q000821:virology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009928:Organ Specificity; D016133:Polymerase Chain Reaction / Q000379:methods; D017378:Quinolinic Acid / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D015215:Zidovudine / Q000627:therapeutic use
D017931:DNA Primers; D004279:DNA, Viral; D014409:Tumor Necrosis Factor-alpha; D015215:Zidovudine; D017378:Quinolinic Acid; D016049:Didanosine