Assembly and Immunogenicity of Chimeric Gag–Env Proteins Derived from the Human Immunodeficiency Virus Type 1
| Autor: | Francis Barin, François Mallet, Catherine Truong, Denys Brand, Sylvie Brunet, Philippe Roingeard |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Recombinant Fusion Proteins
viruses Molecular Sequence Data Immunology Human immunodeficiency virus (HIV) Gene Products gag Biology medicine.disease_cause Epitope Virus law.invention Mice Viral envelope law Virology medicine Animals Humans Amino Acid Sequence Mice Inbred BALB C Base Sequence Immunogenicity Gene Products env Group-specific antigen Molecular biology Infectious Diseases HIV-1 Recombinant DNA Female Immunization Sequence Analysis Epitope Mapping Gene Deletion |
| Zdroj: | AIDS Research and Human Retroviruses. 12:291-301 |
| ISSN: | 1931-8405 0889-2229 |
| Popis: | We evaluated the potential of the precursor Gag protein (Pr55) of the human immunodeficiency virus type 1 (HIV-1) as a carrier for the presentation of envelope epitopes. Recombinant chimeric core-envelope protein-expressing constructs were derived by deletion of regions within the gag gene, especially of regions encoding p24 capsid epitopes. Sequences encoding either the principal neutralization determinant (PND) and/or the CD4-binding domains (CD4BS) were then inserted. Deletion of residues 196-226 within the p24 capsid protein did not prevent self-assembly into virus-like particles (VLPs) whereas deletion of residues 299-328 completely abolished VLP formation. Thus the major homology region (MHR) and proximal sequences are required for capsid assembly. An immunization study in mice showed that assembled chimeric proteins elicited strong anti-Gag, weak anti-envelope, and no neutralizing humoral responses. Nonassembled chimeric proteins were poor immunogens. Mapping of Pr55 antigenic sites using sera from immunized mice and peptides overlapping the entire Gag precursor showed that p24 capsid and p17 matrix epitopes presented to the immune system differed from the mature form (p24 or p17) and the multimeric immature form (Pr55). |
| Databáze: | OpenAIRE |
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