A Disulfide-Bound HIV-1 V3 Loop Sequence on the Surface of Human Rhinovirus 14 Induces Neutralizing Responses against HIV-1
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A. Zhang
Abstract
An immunogenic sequence from the V3 loop of the MN isolate of human immunodeficiency virus type 1 (HIV-1), His-Ile-Gly-Pro-Gly-Arg-Ala-Phe, was transplanted onto a surface loop of the VP2 capsid protein of human rhinovirus 14. To optimize for virus viability and immunogenicity of the transplanted sequence, the HIV sequence was flanked by (1) a cysteine residue that could form a disulfide bond and (2) randomized amino acids (in either of two arrangements) to generate numerous presentations of the Cys-Cys loop. The location for engineering in VP2 was chosen by searching the geometries of disulfide-bound loops in known protein structures. A model for the structure of the transplanted V3 loop sequence was developed using molecular dynamics and energy minimization calculations. Proteolytic digestion with and without reducing agent demonstrated the presence of the disulfide bond in the chimeric virus examined. Monoclonal and polyclonal antibodies directed against the V3 region of the HIV-1MN strain potently neutralized two chimeric viruses. Guinea pig antisera against two chimeric viruses were able to neutralize HIV-1MN and HIV-1ALA-1 in cell culture. The ability of chimeric viruses to elicit antibodies capable of neutralizing the source of the transplanted sequence could be favorable for vaccine development.
Copyright © 1999 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Chimeric Virus-Like Particles as Vaccines
- The Core Antigen of Hepatitis B Virus as a Carrier for Immunogenic Peptides
- Enhancing the Immunogenicity of Exogenous Hepatitis B Surface Antigen-Based Vaccines for MHC-I-Restricted T Cells
- The Role of the Proteasome System and the Proteasome Activator PA28 Complex in the Cellular Immune Response
- Ty Virus-Like Particles, DNA Vaccines and Modified Vaccinia Virus Ankara; Comparisons and Combinations
- Chaperones Involved in Hepatitis B Virus Morphogenesis
- Behavior of a Short preS1 Epitope on the Surface of Hepatitis B Core Particles
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- Development of HIV/AIDS Vaccine Using Chimeric gag-env Virus-Like Particles
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- DNA-Plasmids of HIV-1 Induce Systemic and Mucosal Immune Responses
- Yeast Cells Allow High-Level Expression and Formation of Polyomavirus-Like Particles
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- Site-Specific Fluorescence Labelling of Recombinant Polyomavirus-Like Particles
