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About the Authors:
Sarah I. Daniels
Contributed equally to this work with: Sarah I. Daniels, David A. Davis
Affiliation: HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
David A. Davis
Contributed equally to this work with: Sarah I. Daniels, David A. Davis
* E-mail: [email protected]
Affiliation: HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Erin E. Soule
Affiliation: HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Stephen J. Stahl
Affiliation: Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Irene R. Tebbs
Affiliation: HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Paul Wingfield
Affiliation: Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
Robert Yarchoan
Affiliation: HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Introduction
HIV-1 GagProPol autoprocessing is a unique step in the HIV life cycle and involves the dimerization of two GagProPol monomers and subsequent autocleavage of the polyproteins to generate virus structural proteins as well as protease, reverse transcriptase, and integrase [1]. This autoprocessing is usually delayed until GagProPol and Gag polyproteins assemble at the cell membrane and is followed by further cleavage of Gag and other GagProPol polyproteins during and/or just after budding from the plasma membrane [2], [3]. Premature autoprocessing and activation of protease in HIV-1 infected cells or over-expression of GagProPol, impairs viral production and infectivity [4], [5]. Similar results have been described for Rous sarcoma virus (RSV), where a protease-linked dimer results in premature viral processing in the cytoplasm of infected cells in conjunction with decreased virus production [6]. These studies indicate a need for control over the timing of protease activation, particularly when viral expression and therefore protease are at their highest levels.
Previous studies have demonstrated that reversible oxidation can...