- 作者: Michael Klutch; Amy M. Woerner; Carol J. Marcus-Sekura; Judith G. Levin
- 作者服務機構: a Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, and; b Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md., USA
- 中文摘要: --
- 英文摘要: We have generated peptide antisera against selected regions in HIV-1 and HIV-2 reverse transcriptase (RT) and integrase (IN) to investigate the specificity of determinants governing the immune response. Peptides representing homologous regions (>50%) in the N- and C-termini and central portions of these proteins were synthesized and injected into rabbits. HIV-1 and HIV-2 IN peptide antisera inhibited IN-mediated cleavage of an HIV-1 DNA oligonucleotide substrate in a 3' processing assay, while anti-RT or normal sera had no effect. None of the RT sera inhibited RT activity. In Western blots, HIV-2 antisera directed against RT or IN peptides recognized HIV-2 RT and IN proteins, respectively, as expected, but also cross-reacted with the corresponding HIV-1 proteins. By contrast, corresponding HIV-1 antisera were type-specific. In some cases, HIV-1 cross-reactive antisera could be generated by immunization with HIV-1 chimeric peptides with as few as two residues in the HIV-1 sequence changed to the corresponding HIV-2 amino acids. The finding that a type-specific response can be converted to a cross-reactive response suggests alternate strategies for developing new diagnostic reagents which detect HIV-1 and HIV-2. In addition, our results provide a general model for generating HIV peptide vaccines with dual specificity against HIV-1 and HIV-2.
- 中文關鍵字: --
- 英文關鍵字: HIV-1 ; HIV-2; Synthetic peptides ; Peptide antisera ; Cross-reactive response ; Chimeric peptides ; Reverse transcriptase ; Integrase ; Enzyme assays ; Peptide diagnostics