The AIDS virus, HIV, infects helper T cells through the use of the receptor called CD4 and the coreceptor CCR5 or CXCR4 -- both of these, therefore, represent potential targets to block virus entry. Are there other targets? In Nature Immunology, scientists show that treatment of CD4+ T cells with a reagent that prevents reoxidization of dithiols in CD4 will block HIV entry into the cells.
Disulfide bonds are known to affect the structure, flexibility and function of proteins. Disulfides can be sensitive to the availability of electrons in the environment (that is, sensitive to the “redox state”). The sulfur atoms of disulfides can either form a bridge between two distant parts of a protein or remain unlinked. Philip Hogg and colleagues at the University of New South Wales, Australia, showed that the disulfide bond in a specific domain of CD4 is “redox”-sensitive, with serious consequences. Importantly, fixing the D2 disulfide bond in a reduced state (that is, blocking the formation of the bridge) prevents HIV entry into CD4 T cells. In the natural state, the redox state of D2 is regulated by thioredoxin, an enzyme secreted by activated T cells. This redox pathway could contain new potential targets for inhibitors of HIV entry into T cells.
A News & Views from Mark Goldsmith in Palo Alto, CA puts this work into perspective and will be released at the same time.
Philip J. Hogg
University of New South Wales, Sydney
Tel: +61 2 9385 1004
News & Views contact:
Genencor International, Inc.
Palo Alto, CA
Tel: +1 650 846 7574
Article available online.
(C) Nature Immunology press release.
Message posted by: Trevor M. D'Souza
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