Frequent and early HIV-1MN neutralizing capacity in sera from Dutch HIV-1 seroconverters is related to antibody reactivity to peptides from the gp120 V3 domain

Abstract

The temporal development of HIV-1 neutralizing activity and antibodies to the gp120-V3 neutralization domain were studied in sera from 20 Dutch HIV-1-infected individuals followed from seroconversion on. Serum neutralizing capacity was assessed with three T cell line-tropic isolates: HIV-1MN, HIV-1HXB2, and the patient isolate HIV-1(320). Neutralizing activity to HIV-1MN developed in 18 individuals (90%) within 0 to 10 months after seroconversion. Parallel evolution of IgG reactivity to V3 peptides of United States/European type variants, and the capability of such peptides to completely inhibit HIV-1MN neutralization in four of five tested sera (taken 1-2 years after seroconversion), indicate that a large proportion of HIV-1MN neutralizing antibodies is directed to V3. The early appearance and high frequency of HIV-1MN neutralizing activity in the Dutch study group indicate the close relationship of HIV-1MN to HIV-1 variants circulating in the Netherlands. Neutralizing activity to HIV-1HXB2 (in 15 of 20 individuals) developed several months after that to HIV-1MN in all individuals (average, 10 months after seroconversion) and was not seen in the absence of HIV-1MN neutralizing activity. Neutralizing activity to the Dutch isolate HIV-1(320) (found in 11 of 18 tested individuals) emerged simultaneously with that to HIV-1MN in 4 individuals but appeared later in 7. In most individuals, HIV-1HXB2 neutralization was not accompanied by reactivity to a V3 peptide from this strain, indicating that the extension of neutralizing activity to more divergent strains, which takes place at later stages, must be attributed to non-V3-directed antibodies.