gP120 beta-turn conformation affects immunogenicity of HIV-1 Field Isolates.
Int Conf AIDS 2000 Jul 9-14; 13:33 (abstract no.. LbPeA7006)
Appah Jr F, Lee SK, Samms M, Riley J, Boto W City College of New York, The City College of the University of New York 10031. Fax: 212-650-7989, E-mail: frankappahjr@mail.com.
The results of this study show that HIV-1 field isolates express two distinct conformational variants of gp120. One subset of the isolates (A--UG06c, B-RT3.12, C-UG045) display a strong beta-turn conformation in the V3 loop and the other subset (D-UG23c, D-UG042 and B-RTI.4) are deficient in the expression of a beta-turn in the loop. DNA-mediated immunization of mice with the beta-turn competent rgp120 molecules elicited vigorous antibody and cell-mediated immune responses to the V3 loop. In contrast, immunization with the beta-turn deficient rgp120 was shown to trigger a strong cell-mediated immune response associated with the secretion of IL-2 and IFN-g without evidence of antibody development. Reconstitution of a beta-turn by site-directed mutagenesis yielded gp120 which promoted both antibody and CMI responses to the V3 loop. The results demonstrate a marked impact of sequence variation on secondary structure and antigenic properties of gp120 encoded in divergent HIV- 1 field isolates, and may complement the current search for gloabally effacious DNA vaccines.
Keywords: AEGIS, HIV-1, Molecular Conformation, Vaccines, DNA, Immunization, Variation (Genetics), Animal, Mice, immunology, genetics, AIDS 000709
LbPeA7006
