Cells expressing both human CD4 and a human fusion accessory factor associated with HIV infection

Inactive Publication Date: 2005-03-24
BERGER EDWARD +3
View PDF3 Cites 12 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because they lack this accessory factor, nonhuman cell types engineered to express only human CD4 are incapable of membrane fusion, and are thus nonpermissive for HIV infection.
Without an effective vaccine, the number of individuals infected with HIV will likely increase substantially.
Furthermore

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Cells expressing both human CD4 and a human fusion accessory factor associated with HIV infection
  • Cells expressing both human CD4 and a human fusion accessory factor associated with HIV infection
  • Cells expressing both human CD4 and a human fusion accessory factor associated with HIV infection

Examples

Experimental program
Comparison scheme
Effect test

example 1

Characterization Of CXCR4 Protein

[0109] Based on the known topology of 7-transmembrane segment proteins, four regions of CXCR4 are predicted to be exposed at the cell surface. Synthetic peptides are synthesized by methods well-known in the art that correspond to each of these 4 regions. Rabbit antisera is raised by immunization with peptide-KLH (keyhole limpet hemocyanin) conjugates. Total immunoglobulin is purified from the preimmune and the immune sera by chromatographic separation with Protein-A Sepharose.

[0110] Antibodies raised against the 38 amino acid N-terminal portion of CXCR4 blocked membrane fusion between the env-positive, LAV isolate of HIV-1, and CD4-positive, primary T cells. In contrast, antibodies raised against other peptide-KLH conjugates had no effect of membrane fusion between the virus and the target cells.

example 2

CXCR4-Mediated Inhibition of Viral Fusion

[0111] The sensitivity of fusion mediate by env from different HIV isolates was tested using antibodies against the N-terminal portion of CXCR4. FIG. 2 shows that these anti-CXCR4 antibodies inhibited fusion mediated by the prototypic T cell line-tropic LAV env, but did not inhibit fusion mediated by the prototypic macrophage-tropic Ba-L env. These results indicate that the fusion inhibition with anti-CXCR4 antibodies is not due to nonspecific inhibitory effects on the cells. Table 3 demonstrates that coexpression of CXCR4 enhanced fusion much more with env from T cell line-tropic isolates (IIIB, LAV, and RF) as compared with env from macrophage-tropic strains (Ba-L, SF162, JR-FL, and ADA).

[0112] Although the invention has been described with reference to the presently preferred embodiment, it should be understood that various modifications can be made without departing from the spirit of the invention. Accordingly, the invention is limited...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Dimensionless propertyaaaaaaaaaa
Dimensionless propertyaaaaaaaaaa
Pharmaceutically acceptableaaaaaaaaaa
Login to view more

Abstract

The susceptibility to human immunodeficiency virus (HIV) infection depends on the cell surface expression of the human CD4 molecule and a human fusion accessory factor associated with HIV infection (CXCR4). CXCR4 is a member of the 7-transmembrane segment superfamily of G-protein-coupled cell surface molecules. CXCR4 plays an essential role in the membrane fusion step of HIV infection. The establishment of stable, nonhuman cell lines and transgenic mammals having cells that coexpress human CD4 and CXCR4 provides valuable tools for the continuing research of HIV infection and the development of more effective anti-HIV therapeutics. In addition, antibodies against CXCR4, isolated and purified peptide fragments of CXCR4, and CXCR4-binding biologic agents, capable of blocking membrane fusion between HIV and target cells represent potential anti-HIV therapeutics.

Description

FIELD OF THE INVENTION [0001] The present invention pertains to in vitro and in vivo models for the study of human immunodeficiency virus (HIV) infection and the effectiveness of anti-HIV therapeutics. [0002] The susceptibility to HIV infection depends on the cell surface expression of the human CD4 molecule and a heretofore unidentified human fusion accessory factor. The functional assays described herein identified a molecule, designated CXCR4. The term CXCR4 is preferred, however, the terms fusin or HFAF have also been used to refer to the same molecule. Comparison of the nucleotide sequence of the cDNA encoding CXCR4 against a computer database revealed that CXCR4 is a member of the 7-transmembrane segment superfamily of G-protein-coupled cell surface molecules. Many of the superfamily members function as ligand receptors in relation, for example, to peptide hormones, neurotransmitters, and chemokines. CXCR4 has no known ligand, however, and its function is unknown. [0003] A key...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K38/00A61K48/00C07K14/715C07K16/28C12N5/08
CPCA01K2217/05A61K38/00C07K16/2866C07K14/7158A61K48/00
Inventor BERGER, EDWARDFENG, YUKENNEDY, PAULBRODER, CHRISTOPHER
Owner BERGER EDWARD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap