Immunological characterization of gp120 from New York HIV -1 subtype B isolates.
Item
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Title
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Immunological characterization of gp120 from New York HIV -1 subtype B isolates.
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Identifier
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AAI9969725
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identifier
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9969725
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Creator
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Riley, Janice Patricia.
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Contributor
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Adviser: William Boto
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Date
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2000
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Biochemistry | Biology, Molecular | Health Sciences, Pathology
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Abstract
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Human immunodeficiency virus type-1 (HIV-1) has undergone remarkable genetic divergence over time. The accumulation of mutations is particularly pronounced for the envelope (ENV) gene. This region of the provirus encodes the leading subunit candidate vaccine, gp120. The dynamics of transmission and distribution of divergent strains of the virus are important issues in the current search for promising immunoprophylactic therapies to control the AIDS epidemic. To determine the impact of genetic diversity on the immunogenic properties of gp120 encoded in North American subtype of HIV-1 a 625 bp (C2 to V5) fragment of ENV was amplified and sequenced.;Phylogenetic tree analysis of the nucleotide sequences showed that the ENV clones B_RT1.4, B_RT1.15, B_RT1.17, B_RT1.21, derived from the patient isolate RT1 and the ENV clones B_RT3.6, B_RT3.10, B_RT3.11, B_RT3.12 and B_RT3.15 from the isolate RT3, cluster with the "subtype B" viruses. Marked intra-patient and inter-patient sequence variation was recorded over the region analyzed. To assess the effect of the primary sequence variation on the distribution of linear antigenic epitopes, the complementary software programs SURFACE PLOT and PEPTIDE STRUCTURE were used to analyze the region. Eight analogous but distinct antigenic sites designated E1 through E8 were identified in gp120 derived from RT1 and RT3 despite the marked divergence in the primary (nucleotide and amino acids) sequences. Synthetic peptide comprising the E2[V3] epitope in RT1 and RT3 displayed varying ELISA reactivities with sera from asymptomatic HIV-1 infected New York donors.;To further determine the immunogenic potential of gp120 encoded in the sibling clones of RT3 and RT1 immunizations were conducted with naked ENV plasmids and with V3 loop multiple antigenic, peptides (MAPs) from each isolate. Inoculation with the ENV clones and MAPs from the RT3 isolate elicited antibodies that reacted highly with homologous and heterologous PND peptides in ELISA. In a sharp contrast, inoculation with the ENV plasmid and MAPs from the RT1 derived clones elicited near background level of antibody responses. Further, V3 derived MAPs and DNA-mediated immunization with ENV clones of RT3 generated superior cell-mediated immune response compared to immunization with the RT1 derived clones.;These findings demonstrate a marked impact of sequence variation on the immunogenetic properties of gp120 encoded in these HIV-1 field isolates, and could complement the current search for globally effective vaccine candidates.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
