Novel function of prothymosin alpha as a potent inhibitor of human immunodeficiency virus type 1 gene expression in primary macrophages

Arevik Mosoian, Avelino Teixeira, Anthony A. High, Robert E. Christian, Donald F. Hunt, Jeffrey Shabanowitz, Xinyan Liu, Mary Klotman

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

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 (ProTα), 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 ProTα from an HIV-1-inhibitory fraction of CD8+ cell supernatants removes the inhibitory activity, supporting its role in inhibition via soluble mediators. ProTα 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 ProTα suppresses HIV-1 replication, its activity is target cell specific, and inhibition occurs following viral integration. Native and recombinant ProTα 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 ProTα is not HIV LTR specific.

Original languageEnglish
Pages (from-to)9200-9206
Number of pages7
JournalJournal of Virology
Volume80
Issue number18
DOIs
StatePublished - Sep 2006

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