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

Overview

abstract

  • 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.

publication date

  • May 17, 2010

Research

keywords

  • HIV-1
  • Interferon Type I
  • Protein Precursors
  • Thymosin
  • Toll-Like Receptor 4

Identity

PubMed Central ID

  • PMC2890444

Scopus Document Identifier

  • 77953406240

Digital Object Identifier (DOI)

  • 10.1073/pnas.0914870107

PubMed ID

  • 20479248

Additional Document Info

volume

  • 107

issue

  • 22