Journal of Virology, December 1998, p. 9855-9864, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
INSERM U74,
Received 26 May 1998/Accepted 13 August 1998
Previous studies characterized the third variable (V3) loop of the
envelope gp120 as the principal neutralizing determinant for laboratory
T-cell-line-adapted (TCLA) strains of human immunodeficiency virus type
1 (HIV-1). However, primary viruses isolated from infected individuals
are more refractory to neutralization than TCLA strains, suggesting that qualitatively different neutralizing antibodies may be
involved. In this study, we investigated whether the V3 loop
constitutes a linear target epitope for antibodies neutralizing primary isolates. By using peptides representative of the V3
regions of various primary isolates, an early, relatively specific and persistent antibody response was detected in sera from HIV-infected patients. To assess the relationship between these antibodies and
neutralization, the same peptides were used in competition and
depletion experiments. Addition of homologous V3 peptides led to a
competitive inhibition in the neutralization of the TCLA strain
HIVMN/MT-4 but had no effect on the neutralization of the autologous primary isolate. Similarly, the removal of antibodies that
bind to linear V3 epitopes resulted in a loss of HIVMN/MT-4 neutralization, whereas no decrease in the autologous
neutralization was measured. The different roles of V3-specific
antibodies according to the virus considered were thereby brought to
light. This confirmed the involvement of V3 antibodies in the
neutralization of a TCLA strain but emphasized a more pronounced
contribution of either conformational epitopes or epitopes
outside the V3 loop as targets for antibodies neutralizing primary
HIV-1 isolates. This result underlines the need to focus on new
vaccinal immunogens with epitopes able to induce broadly reactive and
efficient antibodies that neutralize a wide range of primary HIV-1 isolates.
*
Corresponding author. Mailing address: Institut
de Virologie, INSERM U74, 3 rue Koeberlé, 67000 Strasbourg,
France. Phone: 0388566300. Fax: 0388566303. E-mail:
c.moog{at}viro-ulp.u-strasbg.fr.
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