Pattern of antibody response against the V3 loop in children with vertically acquired immunodeficiency virus type 1 (HIV-1) infection.
The principal neutralizing domain (PND) of HIV-1, located within the third variable region (V3) of the gp120 envelope protein, is related to the humoral and cellular immune response. We studied the V3 PND-specific antibody response in 30 children with vertically acquired HIV-1 infection by determining the antibodies that bound synthetic peptides derived from the PND of the HIV-1MN, HIV-1SF-2, HIV-1SC, HIV-1IIIB, HIV-1RF, HIV-1ELI, and HIV-1Z6 virus strains. At a standard antigen concentration, we found that most sera (90%) reacted against PNDMN peptide, but 73.3% also cross-reacted against multiple PNDs. A search for high-affinity/avidity antibodies was conducted in an antigen-limited assay; at lower peptide concentrations, cross-reactivity was restricted to PNDMN and PNDSC in 12 of 22 broadly reactive sera. Sequence analysis of the V3 region of HIV-1 isolates indicated that patients with high-affinity/avidity antibodies to PNDMN and PNDSC had a PND with an internal 12-amino acid sequence (serotype-specific domain, SSD) that was highly homologous (> 90%) with the MN and SC SSD. Broadly reactive sera with low-affinity/avidity antibodies showed a lower degree of homology with the SSD sequence of all tested viral strains. The role of anti-PND antibodies in vertical transmission was further studied in 49 children born to HIV-1-seropositive mothers. No statistical correlation emerged between V3 antibodies and HIV-1 transmission, but we found that maternal V3 antibodies were lost soon after birth. This finding may be relevant to a new serological approach to the early diagnosis of vertically transmitted HIV-1 infection.
De Rossi
A
A
Institute of Oncology, University of Padua, Italy.
Zanotto
C
C
Mammano
F
F
Ometto
L
L
Del Mistro
A
A
Chieco-Bianchi
L
L
D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D000939:Epitopes; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000382:microbiology / Q000635:transmission; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009035:Mothers; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D012703:Serotyping
D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments