Impact of genetic variation on the seroreactivity of linear antigenic epitopes in the divergent HIV-1 subtypes.
Item
-
Title
-
Impact of genetic variation on the seroreactivity of linear antigenic epitopes in the divergent HIV-1 subtypes.
-
Identifier
-
AAI9630497
-
identifier
-
9630497
-
Creator
-
Pestano, Gary Anthony.
-
Contributor
-
Adviser: William Boto
-
Date
-
1996
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Biology, Molecular | Health Sciences, Immunology
-
Abstract
-
The sequence variability reported for the neutralizing epitopes of HIV-1 has presented a major obstacle in the search for candidate vaccine(s) to prevent the escalation of the AIDS epidemic. The objective of this study was to analyze the impact of genetic variation on the major neutralizing determinants in gp120 from the divergent subtypes of HIV-1. The region of ENV analyzed encodes the principal neutralizing determinant (PND) in the V3 loop and the linear CD4 binding site. This region was characterized for seven novel Ugandan clones: UG06c, UG23c, UG042, UG044, UG045, UG0963 and UG0964, and for two New York City isolates: RT1 and RT3.12. Phylogenetic analysis showed that the clones segregated with four distinct HIV-1 subtypes. UG06c and UG0964 clustered with subtype A clones, UG23c, UG042, UG044, and UG0963 clustered with the subtype D viruses, and UG045 was determined to be a subtype C clone. RT1 and RT3.12 were most related to the subtype B clones. Surface probability analyses of the amino acid residues identified at least eight potential antigenic epitopes, designated E1 (C2) to E8 (V5), in the divergent ENV subtypes. ELISA was conducted to determine the in-vivo availability of the predicted surface residues. The reactivities of synthetic peptides with sera from infected blood donors in Uganda, New York and Thailand, confirmed that several antigenic sites are well-conserved in the variant envelope molecules. The most intense reactivity was observed against the majority of the V3 peptides tested. However, negligible antibody reactivities were observed against at least one subset of these peptides. Secondary structure analysis indicated that the presence of a type II {dollar}\beta{dollar}-turn in the apical tetrapeptide of the V3 loop is highly predictive of the antigenicity of the PND peptides. Homology models of the tertiary conformations in the PND indicated that the epitope comprising the GPGRAF hexapeptide is specific for the group B isolates. However, the analogous epitope in many African isolates comprises the conserved IGPG tetrapeptide. This study could complement the search for broadly reactive gp120 candidate vaccines.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
