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Stabilization of HIV-1 Envelope in the CD4-bound Conformation through Specific Cross-linking of a CD4 Mimetic*
- Source :
- Journal of Biological Chemistry, Journal of Biological Chemistry, 2011, 286 (24), pp.21706-21716. ⟨10.1074/jbc.M111.232272⟩, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2011, 286 (24), pp.21706-21716, Journal of Biological Chemistry, 2011, 286 (24), pp.21706-21716
- Publication Year :
- 2011
- Publisher :
- American Society for Biochemistry and Molecular Biology, 2011.
-
Abstract
- CD4 binding on gp120 leads to the exposure of highly conserved regions recognized by the HIV co-receptor CCR5 and by CD4-induced (CD4i) antibodies. A covalent gp120-CD4 complex was shown to elicit CD4i antibody responses in monkeys, which was correlated with control of the HIV virus infection (DeVico, A., Fouts, T., Lewis, G. K., Gallo, R. C., Godfrey, K., Charurat, M., Harris, I., Galmin, L., and Pal, R. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 17477–17482). Because the inclusion of CD4 in a vaccine formulation should be avoided, due to potential autoimmune reactions, we engineered small sized CD4 mimetics (miniCD4s) that are poorly immunogenic and do not induce anti-CD4 antibodies. We made covalent complexes between such an engineered miniCD4 and gp120 or gp140, through a site-directed coupling reaction. These complexes were recognized by CD4i antibodies as well as by the HIV co-receptor CCR5. In addition, they elicit CD4i antibody responses in rabbits and therefore represent potential vaccine candidates that mimic an important HIV fusion intermediate, without autoimmune hazard.
- Subjects :
- CD4-Positive T-Lymphocytes
[SDV.BIO]Life Sciences [q-bio]/Biotechnology
Protein Conformation
Plasma protein binding
HIV Envelope Protein gp120
medicine.disease_cause
Biochemistry
Protein structure
Viral Envelope Proteins
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Cricetinae
Disulfides
ComputingMilieux_MISCELLANEOUS
0303 health sciences
Antigen Presentation
Affinity labeling
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
biology
virus diseases
3. Good health
Molecular mimicry
Cross-Linking Reagents
[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Cricetulus
Antibody
Protein Binding
[CHIM.ANAL] Chemical Sciences/Analytical chemistry
[SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication
Receptors, CCR5
[SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
Antigen presentation
Immunology
CHO Cells
Virus
03 medical and health sciences
[SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology
[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication
[CHIM.ANAL]Chemical Sciences/Analytical chemistry
medicine
Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Cysteine
Molecular Biology
030304 developmental biology
030306 microbiology
Cell Biology
biology.organism_classification
Virology
[SDV.BIO] Life Sciences [q-bio]/Biotechnology
biology.protein
HIV-1
[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology
Subjects
Details
- Language :
- English
- ISSN :
- 00219258 and 1083351X
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry, Journal of Biological Chemistry, 2011, 286 (24), pp.21706-21716. ⟨10.1074/jbc.M111.232272⟩, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2011, 286 (24), pp.21706-21716, Journal of Biological Chemistry, 2011, 286 (24), pp.21706-21716
- Accession number :
- edsair.doi.dedup.....39b2b7eccb13dcf33dad30e83fa8bf2a