High Prevalence of Antibodies to the gp120 V3 Region Principal Neutralizing Determinant of HIV-1_MNin Sera from Africa and the Americas

Abstract

Neutralizing antibodies (NA) against HIV-1MN and HIV-1IIIB, and antibodies binding to synthetic peptides (BA) derived from the gp120 envelope V3 region principal neutralizing determinants (PND) of the HIV-1MN, HIV-1IIIB, and HIV-1Z3 virus strains were assayed in HIV-1 antibody-positive sera from the United States, Haiti, Brazil, Zaire, and Zimbabwe. The ability of soluble PND peptide to block neutralization of the corresponding virus by representative sera was also tested. In each country, NA and BA titers were highest against the HIV-1MN strain, and compared with other countries, NA and BA titers against HIV-1MN were higher in sera from the United States and Haiti. When NA titers were compared with BA titers against either HIV-1MN or HIV-1IIIB, no correlation was found for the HIV-1IIIB strain, but there was a significant correlation for HIV-1MN. Addition of the HIV-1MN strain peptide to a neutralization assay for HIV-1MN resulted in a four- to tenfold reduction in NA titers in sera from the United States, Zaire, and Brazil. The results suggest that HIV-1MN and closely related variants are prevalent in many parts of the world, and that antibodies directed against the PND account for most of the neutralizing activity in sera of infected individuals.

A Variable Region 3 (V3) Mutation Determines a Global Neutralization Phenotype and CD4-Independent Infectivity of a Human Immunodeficiency Virus Type 1 Envelope Associated with a Broadly Cross-Reactive, Primary Virus-Neutralizing Antibody Response

“…Infectivity of R2 and MACS strain 9 for HOS CCR5 ϩ cells that did not express CD4 was increased significantly in each of three experiments by the presence of the 313-4 PM mutation. There was some evidence of infectivity of the MACS strain 3 (313-4HI/PM) clone for HOS CCR5 Peptide blocking studies were carried out to evaluate the possibility that anti-V3 antibodies might contribute to the cross-reactivity of HNS2 (6,46). In preliminary studies it was found that addition of peptide to nonimmune serum did not cause the serum to enhance infectivity of virus pseudotyped with R2 envelope (not shown).…”

“…In one case the peptide was cyclized before lyophilization, as described below. Preparation of a linear MN strain V3 peptide has been described previously (6). Cyclized MN strain 35-mer peptide was obtained from the ARRRP (catalog no.…”

Microarray Profiling of Antibody Responses against Simian-Human Immunodeficiency Virus: Postchallenge Convergence of Reactivities Independent of Host Histocompatibility Type and Vaccine Regimen

“…Seventeen of the 25 convergent peptides include regions that have been described previously as being immunodominant, the V3, Kennedy, Wang, and Gnann epitopes (14,20,27,50,53). Particularly notable was the range of reactivity to the V3 loop, a principal neutralizing and tropism-determining domain (Fig.…”

Escape of HIV-1 is associated with lack of V3 domain-specific antibodies in vivo

“…Also, the V3 loop is the major target for neutralizing [3,4] and enhancing [5][6][7] antibodies, which are part of the immunodominant antibody response in natural and experimental HIV-1 infection [8][9][10][11].…”