Maternofetal transmission of human immunodeficiency virus-1: the role of antibodies to the V3 primary neutralizing domain.
The increase in the number of human immunodeficiency virus-1 (HIV-1)-infected children is a direct consequence of the heterosexual spread of the disease to women and the growing number of HIV-positive i.v. drug users. It is not known how the majority of infants born to HIV-1-infected women escape HIV-1 infection, and, for those infected, the timing of HIV-1 transmission has yet to be determined. In addition, the role of maternal antibodies in the prevention of HIV-1 transmission to the fetus is unclear. We have previously demonstrated a correlation between vertical transmission and the absence of high-affinity/avidity antibodies to a peptide, KRI-HIGPGRAFYT, which corresponds to a region of the primary neutralizing domain of the gp120 V3 loop of HIVMN (MN-PND). The present study examines the correlation between the presence of these high affinity antibodies in women completing a pregnancy or undergoing an elective abortion and the detection of HIV-1 infection in their aborted fetuses. In several instances, transmission occurred despite high-affinity antibodies to the MN-PND. We have, therefore, evaluated the reactivity of sera to different MN-PND variants. In one infant born to a mother with high-affinity/avidity antibodies to KRI-HIGPGRAFYT (classic MN-PND), the infected baby developed antibodies to an MN-PND variant peptide against which his mother did not mount a humoral immune response during pregnancy. This finding indicates that fetal infection with MN-PND escape mutants arising during pregnancy may occur during a period when the mother is serologically negative.
Rubinstein
A
A
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461.
Goldstein
H
H
Calvelli
T
T
Devash
Y
Y
Rubinstein
R
R
Soeiro
R
R
Lyman
W
W
D000595:Amino Acid Sequence; D000915:Antibody Affinity; D005260:Female; D005333:Fetus / Q000382:microbiology; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*
D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D010455:Peptides