title: HIV dementia patients exhibit reduced viral neutralization and increased envelope sequence diversity in blood and brain.
abstract: OBJECTIVE
  To examine the relationship between the humoral immune response and viral envelope diversity among HIV/AIDS patients with or without HIV-associated dementia (HAD).
  
  
  METHODS
  Whole blood and sera were collected from age- and disease-progression matched AIDS-defined patients with and without neuro-cognitive impairment at two centers. Peripheral blood mononuclear cells were isolated from whole blood and separated into monocyte/macrophage and peripheral blood lymphocyte (PBL) preparations. Genomic DNA, isolated from the PBL population, was used as template to amplify HIV-1 C2V3 envelope sequences in a nested PCR protocol. The resulting fragments were sequenced and subjected to a phylogenetic analysis.
  
  
  RESULTS
  Sera from non-demented (ND; n = 21) patients neutralized infection of CCR5-dependent, but not CXCR4-dependent viruses, more efficiently than sera from HAD patients (n = 15) (P < 0.05). A recombinant virus containing a brain derived C2V3 sequence was also neutralized less efficiently by sera from HAD patients ( < 0.05). C2V3 envelope sequences amplified from PBL revealed significantly greater diversity within the V3 region from HAD compared with ND patients (P < 0.001). The number of non-synonymous substitutions was positively correlated with the severity of neuro-cognitive impairment of patients (P < 0.005). Similarly, brain derived V3 sequences exhibited significantly increased diversity among HAD patients (P < 0.001).
  
  
  CONCLUSIONS
  Our findings imply that HAD patients exhibited impaired serological responses that may lead to the emergence of viral mutants that potentially could infect the brain and mediate neurodegeneration.
mesh_terms: D015526:AIDS Dementia Complex / Q000209:etiology / Q000473:pathology / Q000821:virology*; D001812:Blood-Brain Barrier; D001921:Brain / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D015752:Genes, env; D014644:Genetic Variation; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D017421:Sequence Analysis
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral