Novel function of prothymosin alpha as a potent inhibitor of human immunodeficiency virus type 1 gene expression in primary macrophages.
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.
Mosoian
Arevik
A
Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, Box 1090, New York, NY 10029, USA.
Teixeira
Avelino
A
High
Anthony A
AA
Christian
Robert E
RE
Hunt
Donald F
DF
Shabanowitz
Jeffrey
J
Liu
Xinyan
X
Klotman
Mary
M
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
D019380:Anti-HIV Agents; D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin