BIOMAT Database Logo BIOMAT Database Logo

Adaptation to blockade of human immunodeficiency virus type 1 entry imposed by the anti-CCR5 monoclonal antibody 2D7. 2001

E J Aarons, and S Beddows, and T Willingham, and L Wu, and R A Koup
Department of Medicine, Division of Infectious Disease, University of Texas Southwestern Medical Center, Texas, Dallas 75390, USA.

The second extracellular loop (ECL2) domain of CC-chemokine receptor 5 (CCR5) has been proposed as a specific target site for therapeutic agents aimed at blocking CCR5-dependent entry by human immunodeficiency virus type I (HIV-1). We have adapted two CCR5-using HIV-1 isolates, prototypic JR-CSF, and a primary isolate, 11-121, to replicate in vitro in the presence of high concentrations of a monoclonal antibody (MAb 2D7) specific for the CCR5 ECL2 domain. The 75% inhibitory concentrations (IC(75)) for the two 2D7-adapted isolates were approximately 100-fold higher than those for corresponding control isolates passaged without the MAb. Adapted isolates did not acquire the ability to use CXCR4, CCR3, or CCR1. Env clones derived from MAb 2D7-adapted JR-CSF showed several gp120 mutations that were not found in any of the control JR-CSF clones. The in vitro observations suggest that CCR5-using HIV-1 strains might also be able to adapt in vivo to evade an ECL2-blocking therapeutic agent.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003001 Cloning, Molecular The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells. Molecular Cloning
D005814 Genes, Viral The functional hereditary units of VIRUSES. Viral Genes,Gene, Viral,Viral Gene
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000220 Adaptation, Biological Changes in biological features that help an organism cope with its ENVIRONMENT. These changes include physiological (ADAPTATION, PHYSIOLOGICAL), phenotypic and genetic changes. Adaptation, Biologic,Biological Adaptation,Biologic Adaptation
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015699 HIV Envelope Protein gp120 External envelope protein of the human immunodeficiency virus which is encoded by the HIV env gene. It has a molecular weight of 120 kDa and contains numerous glycosylation sites. Gp120 binds to cells expressing CD4 cell-surface antigens, most notably T4-lymphocytes and monocytes/macrophages. Gp120 has been shown to interfere with the normal function of CD4 and is at least partly responsible for the cytopathic effect of HIV. Envelope Glycoprotein gp120, HIV,HTLV-III gp120,env Protein gp120, HIV,gp120(HIV),HIV Envelope Glycoprotein gp120,gp120 Envelope Glycoprotein, HIV,HTLV III gp120,gp120, HTLV-III

Related Publications

E J Aarons, and S Beddows, and T Willingham, and L Wu, and R A Koup
An anti-CCR5 monoclonal antibody and small molecule CCR5 antagonists synergize by inhibiting different stages of human immunodeficiency virus type 1 entry.
September 2006, Virology,
E J Aarons, and S Beddows, and T Willingham, and L Wu, and R A Koup
Potent, broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140.
January 2001, Journal of virology,
E J Aarons, and S Beddows, and T Willingham, and L Wu, and R A Koup
Identification of a linear peptide recognized by monoclonal antibody 2D7 capable of generating CCR5-specific antibodies with human immunodeficiency virus-neutralizing activity.
June 2005, Journal of virology,
E J Aarons, and S Beddows, and T Willingham, and L Wu, and R A Koup
Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody.
December 1992, Journal of virology,
E J Aarons, and S Beddows, and T Willingham, and L Wu, and R A Koup
Potent antiviral synergy between monoclonal antibody and small-molecule CCR5 inhibitors of human immunodeficiency virus type 1.
October 2006, Antimicrobial agents and chemotherapy,
E J Aarons, and S Beddows, and T Willingham, and L Wu, and R A Koup
Inhibition of interleukin-6-induced human immunodeficiency virus type 1 expression by anti-gp130 monoclonal antibody.
November 1997, Biochemistry and molecular biology international,
E J Aarons, and S Beddows, and T Willingham, and L Wu, and R A Koup
Maraviroc, a CCR5 coreceptor antagonist that blocks entry of human immunodeficiency virus type 1.
March 2009, Pharmacotherapy,
E J Aarons, and S Beddows, and T Willingham, and L Wu, and R A Koup
Neutralization of primary human immunodeficiency virus type 1 isolates by the broadly reactive anti-V3 monoclonal antibody, 447-52D.
November 1994, Journal of virology,
E J Aarons, and S Beddows, and T Willingham, and L Wu, and R A Koup
Blockade of human immunodeficiency virus type 1 expression by caveolin-1.
September 2002, Journal of virology,
E J Aarons, and S Beddows, and T Willingham, and L Wu, and R A Koup
GATA-1 transcription factor transactivates the promoter for CCR5, a coreceptor for human immunodeficiency virus type 1 entry.
February 1999, Blood,
Copied contents to your clipboard!