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A soluble factor(s) secreted from CD8(+) T lymphocytes inhibits human immunodeficiency virus type 1 replication through STAT1 activation.

Publication ,  Journal Article
Chang, TL-Y; Mosoian, A; Pine, R; Klotman, ME; Moore, JP
Published in: J Virol
January 2002

CD8(+) T lymphocytes can suppress 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. However, the mechanism by which CAF inhibits LTR activation is not understood. Here, we show that conditioned media from several herpesvirus saimari-transformed CD8(+) T lymphocytes inhibit, in a time- and dose-dependent manner, the replication of HIV-1 pseudotype viruses that express the envelope glycoproteins of vesicular stomatitis virus (HIV-1(VSV)). The same conditioned media also inhibit phorbol myristate acetate-induced activation of the HIV-1 LTR and activate the signal transducer and activator of transcription 1 (STAT1) protein. We have obtained direct evidence that STAT1 is necessary for CAF-mediated inhibition of LTR activation and HIV-1 replication. Thus, the inhibitory effect of CAF on HIV-1(VSV) replication was abolished in STAT1-deficient cells. Moreover, CAF inhibition of LTR activation was diminished both in STAT1-deficient cells and in cells expressing a STAT1 dominant negative mutant but was restored when STAT1 was reintroduced into the STAT1-deficient cells. We also observed that CAF induced the expression of interferon regulatory factor 1 (IRF-1), and that IRF-1 gene induction was STAT-1 dependent. Taken together, our results suggest that CAF activates STAT1, leading to IRF-1 induction and inhibition of gene expression regulated by the HIV-1 LTR. This study therefore helps clarify one molecular mechanism of host defense against HIV-1.

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Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

January 2002

Volume

76

Issue

2

Start / End Page

569 / 581

Location

United States

Related Subject Headings

  • Virus Replication
  • Virology
  • Transfection
  • Transcriptional Activation
  • Trans-Activators
  • Time Factors
  • Tetradecanoylphorbol Acetate
  • Solubility
  • STAT1 Transcription Factor
  • Protein Binding
 

Citation

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Chang, T.-Y., Mosoian, A., Pine, R., Klotman, M. E., & Moore, J. P. (2002). A soluble factor(s) secreted from CD8(+) T lymphocytes inhibits human immunodeficiency virus type 1 replication through STAT1 activation. J Virol, 76(2), 569–581. https://doi.org/10.1128/jvi.76.2.569-581.2002
Chang, Theresa Li-Yun, Arevik Mosoian, Richard Pine, Mary E. Klotman, and John P. Moore. “A soluble factor(s) secreted from CD8(+) T lymphocytes inhibits human immunodeficiency virus type 1 replication through STAT1 activation.J Virol 76, no. 2 (January 2002): 569–81. https://doi.org/10.1128/jvi.76.2.569-581.2002.
Chang, Theresa Li-Yun, et al. “A soluble factor(s) secreted from CD8(+) T lymphocytes inhibits human immunodeficiency virus type 1 replication through STAT1 activation.J Virol, vol. 76, no. 2, Jan. 2002, pp. 569–81. Pubmed, doi:10.1128/jvi.76.2.569-581.2002.

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

January 2002

Volume

76

Issue

2

Start / End Page

569 / 581

Location

United States

Related Subject Headings

  • Virus Replication
  • Virology
  • Transfection
  • Transcriptional Activation
  • Trans-Activators
  • Time Factors
  • Tetradecanoylphorbol Acetate
  • Solubility
  • STAT1 Transcription Factor
  • Protein Binding