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Journal of Virology, June 2003, p. 6777-6784, Vol. 77, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.12.6777-6784.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

CAF-Mediated Human Immunodeficiency Virus (HIV) Type 1 Transcriptional Inhibition Is Distinct from {alpha}-Defensin-1 HIV Inhibition

Theresa Li-Yun Chang, Fleur François, Arevik Mosoian, and Mary E. Klotman*

Departments of Medicine and Microbiology, Mount Sinai School of Medicine, New York, New York

Received 4 December 2002/ Accepted 19 March 2003

CD8+ T lymphocytes can inhibit human immunodeficiency virus type 1 (HIV-1) replication by secreting a soluble factor(s) known as CD8+ T-lymphocyte antiviral factor (CAF). One site of CAF action is inhibition of HIV-1 RNA transcription, particularly at the step of long terminal repeat (LTR)-driven gene expression. The inhibitory effect of CAF on HIV-1 LTR activation is mediated through STAT1 activation. A recent study reports that {alpha}-defensins 1 to 3 account for CAF activity against HIV-1. Here, we address whether {alpha}-defensins, particularly {alpha}-defensin-1, contribute to CAF-mediated inhibition of HIV-1 transcription. Both recombinant {alpha}-defensin-1 and CAF derived from herpesvirus saimiri (HVS)-transformed CD8+ cells inhibited HIV-1 infection and gene expression. For both factors, the inhibition of HIV-1 infection did not occur at the level of viral entry. Pretreatment of cells with {alpha}-defensin-1 followed by a washing out prior to infection blocked infection by HIV-1, indicating that direct inactivation of virions was not required for its inhibitory effect. In contrast to CAF, {alpha}-defensin-1 did not inhibit phorbol myristate acetate- or Tat-mediated HIV-1 LTR activation in a transient transfection system, nor did it activate STAT1 tyrosine phosphorylation. Furthermore, {alpha}-defensins 1 to 3 were below the level of detection in a panel of HVS-transformed CD8+ cells with potent HIV-1 inhibitory activity and a neutralizing antibody against {alpha}-defensins 1 to 3 did not reverse the inhibitory effect of CAF on HIV-1 gene expression in infected cells and on HIV-1 LTR activation in transfected cells. Taken together, our results suggest that {alpha}-defensin-1 inhibits HIV-1 infection following viral entry but that {alpha}-defensins 1 to 3 are not responsible for the HIV-1 transcriptional inhibition by CAF.

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

Journal of Virology, June 2003, p. 6777-6784, Vol. 77, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.12.6777-6784.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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