Publications & Reports

Disulfide exchange in domain 2 of CD4 is required for entry of HIV-1.

Lisa J Matthias, Patricia T W Yam, Xing-Mai Jiang, Nick Vandegraaff, Peng Li, Pantelis Poumbourios, Neil Donoghue, Philip J Hogg
Centre for Thrombosis and Vascular Research, School of Medical Sciences, University of New South Wales and Department of Haematology, Prince of Wales Hospital, Sydney, NSW 2052, Australia.


CD4, a member of the immunoglobulin superfamily of receptors that mediates cell-cell interactions in the immune system, is the primary receptor for HIV-1. The extracellular portion of CD4 is a concatenation of four immunoglobulin-like domains, D1 to D4. The D1, D2 and D4 domains each contain a disulfide bond. We show here that the D2 disulfide bond is redox-active. The redox state of the thiols (disulfide versus dithiol) appeared to be regulated by thioredoxin, which is secreted by CD4(+) T cells. Locking the CD4 and the thioredoxin active-site dithiols in the reduced state with a hydrophilic trivalent arsenical blocked entry of HIV-1 into susceptible cells. These findings indicate that redox changes in CD4 D2 are important for HIV-1 entry and represent a new target for HIV-1 entry inhibitors.


  • Journal: Nature immunology
  • Published: 01/08/2002
  • Volume: 3
  • Issue: 8
  • Pagination: 727-732


Health Issue