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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 May 10;91(10):4559–4563. doi: 10.1073/pnas.91.10.4559

Inhibition of human immunodeficiency virus infection by agents that interfere with thiol-disulfide interchange upon virus-receptor interaction.

H J Ryser 1, E M Levy 1, R Mandel 1, G J DiSciullo 1
PMCID: PMC43825  PMID: 8183947

Abstract

The cell surface of mammalian cells is capable of reductively cleaving disulfide bonds of exogenous membrane-bound macromolecules (for instance, the interchain disulfide of diphtheria toxin), and inhibiting this process with membrane-impermeant sulfhydryl reagents prevents diphtheria toxin cytotoxicity. More recently it was found that the same membrane function can be inhibited by bacitracin, an inhibitor of protein disulfide-isomerase (PDI), and by monoclonal antibodies against PDI, suggesting that PDI catalyzes a thiol-disulfide interchange between its thiols and the disulfides of membrane-bound macromolecules. We provide evidence that the same reductive process plays a role in the penetration of membrane-bound human immunodeficiency virus (HIV) and show that HIV infection of human lymphoid cells is markedly inhibited by the membrane-impermeant sulfhydryl blocker 5,5'-dithiobis(2-nitrobenzoic acid), by bacitracin, and by anti-PDI antibodies. The results imply that HIV and its target cell engage in a thiol-disulfide interchange mediated by PDI and that the reduction of critical disulfides in viral envelope glycoproteins may be the initial event that triggers conformational changes required for HIV entry and cell infection. These findings suggest additional approaches to impede cell infection by HIV.

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Selected References

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