Intracellular immunization against HIV infection with an intracellular antibody that mimics HIV integrase binding to the cellular LEDGF protein.
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Date
2017-12-04ICR Author
Author
Bao, L
Hannon, C
Cruz-Mignoni, A
Ptchelkine, D
Sun, M-Y
Miller, A
Bunjobpol, W
Quevedo, CE
Derveni, M
Chambers, J
Simmons, A
Phillips, SEV
Rabbitts, TH
Type
Journal Article
Metadata
Show full item recordAbstract
Preventing the protein-protein interaction of the cellular chromatin binding protein Lens Epithelium-Derived Growth Factor (LEDGF) and human immunodeficiency virus (HIV) integrase is an important possible strategy for anti-viral treatment for AIDS. We have used Intracellular Antibody Capture technology to isolate a single VH antibody domain that binds to LEDGF. The crystal structure of the LEDGF-VH complex reveals that the single domain antibody mimics the effect of binding of HIV integrase to LEDGF which is crucial for HIV propagation. CD4-expressing T cell lines were constructed to constitutively express the LEDGF-binding VH and these cells showed interference with HIV viral replication, assayed by virus capsid protein p24 production. Therefore, pre-conditioning cells to express antibody fragments confers effective intracellular immunization for preventing chronic viral replication and can be a way to prevent HIV spread in infected patients. This raises the prospect that intracellular immunization strategies that focus on cellular components of viral integrase protein interactions can be used to combat the problems associated with latent HIV virus re-emergence in patients. New genome editing development, such as using CRISPR/cas9, offer the prospect intracellularly immunized T cells in HIV+ patients.
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Subject
CD4-Positive T-Lymphocytes
Jurkat Cells
Animals
Humans
Mice
HIV Infections
HIV Integrase
Intercellular Signaling Peptides and Proteins
HIV Core Protein p24
Crystallography, X-Ray
Two-Hybrid System Techniques
Sequence Alignment
Virus Replication
Binding Sites
Amino Acid Sequence
Protein Binding
Molecular Dynamics Simulation
Single-Domain Antibodies
Research team
Chromosomal Translocations and Intracellular Antibody Therapeutics
Language
eng
Date accepted
2017-11-15
License start date
2017-12-04
Citation
Scientific reports, 2017, 7 (1), pp. 16869 - ?
Publisher
NATURE PORTFOLIO