Reduced Monomeric CD4 Is the Preferred Receptor for HIV

• Published in: The Journal of biological chemistry 2010-12, Vol.285 (52), p.40793-40799
• Main Authors: Matthias, Lisa J., Azimi, Iman, Tabrett, Catherine A., Hogg, Philip J.
• Format: Article
• Language: English
• Subjects: AIDS; Alanine; Antigen-presenting cells; CD4; CD4 antigen; CD4 Antigens - genetics; CD4 Antigens - metabolism; Cell fusion; Cell membranes; Cell surface; Cysteine; Cysteine - genetics; Cysteine - metabolism; Disulfide; Disulfide bonds; Disulfides - metabolism; HEK293 Cells; HIV; HIV-1 - genetics; HIV-1 - metabolism; Human immunodeficiency virus 1; Humans; Immunodeficiency; Immunology; Lymphocytes T; Monomers; Protein Multimerization; Protein Structure, Tertiary; Thiol; Virus Internalization
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.190579

CD4 is a co-receptor for binding of T cells to antigen-presenting cells and the primary receptor for the human immunodeficiency virus type 1 (HIV). CD4 exists in three different forms on the cell surface defined by the state of the domain 2 cysteine residues: an oxidized monomer, a reduced monomer, and a covalent dimer linked through the domain 2 cysteines. The disulfide-linked dimer is the preferred immune co-receptor. The form of CD4 that is preferred by HIV was examined in this study. HIV entry and envelope-mediated cell-cell fusion were tested using cells expressing comparable levels of wild-type or disulfide bond mutant CD4 in which the domain 2 cysteines were mutated to alanine. Eliminating the domain 2 disulfide bond increased entry of HIV reporter viruses and enhanced HIV envelope-mediated cell-cell fusion 2–4-fold. These observations suggest that HIV enters susceptible cells preferably through monomeric reduced CD4, whereas dimeric CD4 is the preferred receptor for binding to antigen-presenting cells. Cleavage of the domain 2 disulfide bond is possibly involved in the conformational change in CD4 associated with fusion of the HIV and cell membranes.