Correlation of Titer of Antibody to Principal Neutralizing Domain of HIV MN Strain with Disease Progression in Japanese Hemophiliacs Seropositive for HIV Type 1

Abstract

With the use of the principal neutralizing determinant (PND) peptide-based ELISA to measure anti-PND antibodies that specifically bound synthetic peptides derived from HIV_IIIB, HIV_MN, HIV_RF, HIV_SC, HIV_WJM2, HIV_Af1.con, or HIV_Af2.con, type-specific antibodies to the HIV_MN peptide were studied in 350 serum specimens from Japanese with hemophilia A who had been injected with known unheated factor VIII concentrates until 1985 and had been infected with HIV-1 subtype B. These antibodies were not found in any of the seronegative sera of hemophiliacs, patients with autoimmune diseases, or normal healthy controls. Further, all hemophiliacs rapidly progressing to AIDS and death among the 95 hemophiliacs in a restricted Nara area had antibody titers of less than 20 and their low levels preceded the rapid progression to the disease state. In contrast, slowly progressing hemophiliacs maintained an antibody titer of more than 100 from the initial stages of viral infection and remained asymptomatic. Sequence analysis of the V3 regions of HIV-1 indicated that the hemophiliacs who maintained a high anti-PND_MN antibody level showed a conserved MN sequence. In contrast, the HIV-infected hemophiliacs with nonreactivity in the ELISA showed sequence changes in the neutralizing epitopes of HIV_MN. The dynamic of the serum anti-PNDMN antibody titer appear to be a characteristic indicator of the progression of the HIV-infected status in Japanese hemophiliacs seropositive for HIV-1.