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Prothymosin-alpha inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction.

Publication ,  Journal Article
Mosoian, A; Teixeira, A; Burns, CS; Sander, LE; Gusella, GL; He, C; Blander, JM; Klotman, P; Klotman, ME
Published in: Proc Natl Acad Sci U S A
June 1, 2010

Induction of type I interferons (IFN) is a central feature of innate immune responses to microbial pathogens and is mediated via Toll-like receptor (TLR)-dependent and -independent pathways. Prothymosin-alpha (ProTalpha), a small acidic protein produced and released by CD8(+) T cells, inhibits HIV-1, although the mechanism for its antiviral activity was not known. We demonstrate that exogenous ProTalpha acts as a ligand for TLR4 and stimulates type I IFN production to potently suppress HIV-1 after entry into cells. These activities are induced by native and recombinant ProTalpha, retained by an acidic peptide derived from ProTalpha, and lost in the absence of TLR4. Furthermore, we demonstrate that ProTalpha accounts for some of the soluble postintegration HIV-1 inhibitory activity long ascribed to CD8(+) cells. Thus, a protein produced by CD8(+) T cells of the adaptive immune system can exert potent viral suppressive activity through an innate immune response. Understanding the mechanism of IFN induction by ProTalpha may provide therapeutic leads for IFN-sensitive viruses.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

June 1, 2010

Volume

107

Issue

22

Start / End Page

10178 / 10183

Location

United States

Related Subject Headings

  • Virus Replication
  • Tumor Necrosis Factor-alpha
  • Toll-Like Receptor 4
  • Thymosin
  • Sequence Homology, Amino Acid
  • Recombinant Proteins
  • RNA, Messenger
  • Protein Precursors
  • Myeloid Differentiation Factor 88
  • Molecular Sequence Data
 

Citation

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Mosoian, A., Teixeira, A., Burns, C. S., Sander, L. E., Gusella, G. L., He, C., … Klotman, M. E. (2010). Prothymosin-alpha inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction. Proc Natl Acad Sci U S A, 107(22), 10178–10183. https://doi.org/10.1073/pnas.0914870107
Mosoian, Arevik, Avelino Teixeira, Colin S. Burns, Leif E. Sander, G Luca Gusella, Cijiang He, J Magarian Blander, Paul Klotman, and Mary E. Klotman. “Prothymosin-alpha inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction.Proc Natl Acad Sci U S A 107, no. 22 (June 1, 2010): 10178–83. https://doi.org/10.1073/pnas.0914870107.
Mosoian A, Teixeira A, Burns CS, Sander LE, Gusella GL, He C, et al. Prothymosin-alpha inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10178–83.
Mosoian, Arevik, et al. “Prothymosin-alpha inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction.Proc Natl Acad Sci U S A, vol. 107, no. 22, June 2010, pp. 10178–83. Pubmed, doi:10.1073/pnas.0914870107.
Mosoian A, Teixeira A, Burns CS, Sander LE, Gusella GL, He C, Blander JM, Klotman P, Klotman ME. Prothymosin-alpha inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10178–10183.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

June 1, 2010

Volume

107

Issue

22

Start / End Page

10178 / 10183

Location

United States

Related Subject Headings

  • Virus Replication
  • Tumor Necrosis Factor-alpha
  • Toll-Like Receptor 4
  • Thymosin
  • Sequence Homology, Amino Acid
  • Recombinant Proteins
  • RNA, Messenger
  • Protein Precursors
  • Myeloid Differentiation Factor 88
  • Molecular Sequence Data