title: Measurement of cerebrospinal fluid antibody to the HIV-1 principal neutralizing determinant (V3 loop).
abstract: Antibody to the human immunodeficiency virus (HIV)-1 principal neutralizing determinant (V3 loop) was measured by peptide enzyme-linked immunosorbent assay (ELISA) in cerebrospinal fluid (CSF) and paired serum samples of 21 HIV-seropositive patients. These patients had normal neurologic examinations and were without neurologic symptoms. Peptide ELISA demonstrated intrathecal antibody synthesis against the V3 loop of HIVMN, the V3 loop of HIVNY5, the V3 loop of HIVLAI, and the entire recombinant HIV-1MN gp120 in 21 of 21, 10 of 21, one of 21, and 12 of 21 patients, respectively. Biospecific interaction analysis (BIAcore), which requires only small amounts of CSF, was also used to detect anti-V3 CSF antibody. Fine mapping of linear epitopes within the V3 region was successful in three of five patients by Geysen PIN (PEPSCAN) ELISA and discordance between epitope specificity of CSF and serum antibody was found. While detection of CSF antibody against the V3 loop of HIVMN by peptide ELISA has been recently reported, we add to this finding using the peptide ELISA, PEPSCAN and BIAcore methodologies as well as measuring intrathecal antibody synthesis against V3 loops from HIV strains. Application of these techniques to future studies of anti-V3 antibody in CSF from persons receiving anti-HIV-1 immunizations may provide insight into the immunoregulation of the virus in the nervous system.
authors.affiliation: Department of Retroviral Research, Walter Reed Army Institute of Research, Rockville, Maryland.
authors.forename: D R
authors.initials: DR
authors.lastname: Lucey
authors.forename: T C
authors.initials: TC
authors.lastname: VanCott
authors.forename: L D
authors.initials: LD
authors.lastname: Loomis
authors.forename: F R
authors.initials: FR
authors.lastname: Bethke
authors.forename: C W
authors.initials: CW
authors.lastname: Hendrix
authors.forename: G P
authors.initials: GP
authors.lastname: Melcher
authors.forename: R R
authors.initials: RR
authors.lastname: Redfield
authors.forename: D L
authors.initials: DL
authors.lastname: Birx
mesh_terms: D000595:Amino Acid Sequence; D000918:Antibody Specificity; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood / Q000134:cerebrospinal fluid*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D006679:HIV Seropositivity / Q000134:cerebrospinal fluid* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011994:Recombinant Proteins