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

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...

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, in the absence of effective therapy, most individuals infected with HIV will develop acquired immune deficiency syndrome (AIDS) and succumb to either opportunistic infections and malignancies that result from the deterioration of the immune system, or the direct pathogenic effects of the virus.

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