Rapid Uptake and Inhibition of Viral Propagation by Extracellular OAS1

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Karthiga Thavachelvam
  • ,
  • Hans Henrik Gad
  • Mikkel Søes Ibsen
  • ,
  • Philippe Desprès, Unité Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, Paris, France, Frankrig
  • Marianne Hokland
  • Rune Hartmann
  • Helle Kristiansen, Danmark

The oligoadenylate synthetase (OAS) proteins are traditionally considered intracellular antiviral proteins that mediate antiviral activity through the synthesis of 2'-5'-linked oligoadenylates and subsequent activation of the endoribonuclease RNase L. However, we have recently demonstrated that exogenous recombinant OAS1 is taken up by cells and reduces viral replication both in cell culture and in vivo, independent of RNase L. These results demonstrate a novel paracrine antiviral activity of OAS working in parallel with the classical RNase L pathway. In this study, we investigate the uptake kinetics of recombinant porcine OAS1 and show that it is rapidly and efficiently internalized in a manner that can be blocked by heparin. Heparin, furthermore, abolishes the antiviral activity of OAS1, demonstrating the requirement of the intracellular localization of OAS1 to inhibit the virus. In addition, we demonstrate that exogenous OAS1 affects an early step of the viral replication cycle.

TidsskriftJournal of Interferon & Cytokine Research
Sider (fra-til)359-366
Antal sider8
StatusUdgivet - 5 maj 2015

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