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Journal of Virology, September 2006, p. 9200-9206, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00589-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Novel Function of Prothymosin Alpha as a Potent Inhibitor of Human Immunodeficiency Virus Type 1 Gene Expression in Primary Macrophages

Arevik Mosoian ,1,{dagger} Avelino Teixeira,2,{dagger} Anthony A. High,3,§ Robert E. Christian,3 Donald F. Hunt,3,4,¶ Jeffrey Shabanowitz,3 Xinyan Liu,1 and Mary Klotman1*

Mount Sinai School of Medicine, Department of Medicine, Division of Infectious Diseases, New York, New York 10029,1 Mount Sinai School of Medicine, Department of Medicine, Division of Nephrology, New York, New York 10029,2 Department of Chemistry, University of Virginia, McCormick Road, Charlottesville, Virginia 22901and Department of Pathology, University of Virginia Health Sciences Center, Charlottsville, Virginia 229083

Received 23 March 2006/ Accepted 21 June 2006

CD8+ T lymphocytes control human immunodeficiency virus type 1 (HIV-1) infection by a cytotoxic major histocompatibility complex-restricted pathway as well as by secretion of noncytotoxic soluble inhibitory factors. Several components of CD8+ cell supernatants have been identified that contribute to the latter activity. In this study we report that prothymosin alpha (ProT{alpha}), a protein found in the cell culture medium of the herpesvirus saimiri-transformed CD8+ T-cell line, K#1 50K, has potent HIV-1-inhibitory activity. Depletion of native ProT{alpha} from an HIV-1-inhibitory fraction of CD8+ cell supernatants removes the inhibitory activity, supporting its role in inhibition via soluble mediators. ProT{alpha} is an abundant, acidic peptide that has been reported to be localized in the nucleus and associated with cell proliferation and activation of transcription. In this report we demonstrate that ProT{alpha} suppresses HIV-1 replication, its activity is target cell specific, and inhibition occurs following viral integration. Native and recombinant ProT{alpha} protein potently inhibit HIV-1 long terminal repeat (LTR)-driven gene expression in macrophages. Furthermore studies using different promoters in lentiviral vectors (cytomegalovirus and phosphoglycerate kinase) revealed that suppression of viral replication by ProT{alpha} is not HIV LTR specific.

* Corresponding author. Mailing address: Mount Sinai School of Medicine, Box 1090, New York, NY 10029. Phone: (212) 241-2950. Fax: (212) 534-3240. E-mail: Mary.klotman{at}mssm.edu.

{dagger} These authors contributed equally to this work.

§ Present address: St. Jude Children's Research Hospital, Hartwell Center for Bioinformatics and Biotechnology, Memphis, TN 38105-2794.

Present address: Applied Biosystems, Charlottesville, VA 22901.

Journal of Virology, September 2006, p. 9200-9206, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00589-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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