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Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay
Published on: September 14, 2014
Reduced monomeric CD4 is the preferred receptor for HIV
Lisa J Matthias1, Iman Azimi, Catherine A Tabrett
1Lowy Cancer Research Centre and Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.
The Journal of Biological Chemistry
|October 27, 2010
Summary
Human immunodeficiency virus type 1 (HIV) entry into cells is enhanced by monomeric reduced CD4, not the dimeric form preferred by T cells. Disulfide bond cleavage in CD4 may facilitate HIV and cell membrane fusion.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- CD4 serves as a co-receptor for T cell interactions with antigen-presenting cells.
- CD4 also functions as the primary receptor for human immunodeficiency virus type 1 (HIV).
- Cell surface CD4 exists in monomeric (oxidized or reduced) and dimeric forms, distinguished by domain 2 cysteine residues.
Purpose of the Study:
- To investigate which form of CD4 is preferentially utilized by HIV for entry and fusion.
- To compare HIV entry and cell-cell fusion mediated by wild-type CD4 versus CD4 mutants lacking the domain 2 disulfide bond.
Main Methods:
- Utilized cells expressing comparable levels of wild-type or disulfide bond mutant CD4.
- Assessed HIV entry using reporter viruses.
- Measured HIV envelope-mediated cell-cell fusion.
Main Results:
- Eliminating the domain 2 disulfide bond in CD4 increased HIV reporter virus entry by 2-4 fold.
- Mutant CD4 lacking the disulfide bond enhanced HIV envelope-mediated cell-cell fusion 2-4 fold.
- Dimeric CD4 is the preferred co-receptor for T cell binding to antigen-presenting cells.
Conclusions:
- HIV appears to preferentially enter cells via monomeric reduced CD4.
- Dimeric CD4 is the preferred form for immune co-receptor function.
- Disulfide bond cleavage in CD4 may be crucial for the conformational changes leading to HIV and cell membrane fusion.
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