title: Novel function of prothymosin alpha as a potent inhibitor of human immunodeficiency virus type 1 gene expression in primary macrophages.
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 (ProTalpha), 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 ProTalpha from an HIV-1-inhibitory fraction of CD8(+) cell supernatants removes the inhibitory activity, supporting its role in inhibition via soluble mediators. ProTalpha 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 ProTalpha suppresses HIV-1 replication, its activity is target cell specific, and inhibition occurs following viral integration. Native and recombinant ProTalpha 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 ProTalpha is not HIV LTR specific.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, Box 1090, New York, NY 10029, USA.
authors.forename: Arevik
authors.initials: A
authors.lastname: Mosoian
authors.forename: Avelino
authors.initials: A
authors.lastname: Teixeira
authors.forename: Anthony A
authors.initials: AA
authors.lastname: High
authors.forename: Robert E
authors.initials: RE
authors.lastname: Christian
authors.forename: Donald F
authors.initials: DF
authors.lastname: Hunt
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shabanowitz
authors.forename: Xinyan
authors.initials: X
authors.lastname: Liu
authors.forename: Mary
authors.initials: M
authors.lastname: Klotman
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000821:virology*; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000502:physiology*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000502:physiology; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin