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Published on: December 21, 2019
Proteinase 2Apro is essential for enterovirus replication in type I interferon-treated cells
Juliet M Morrison1, Vincent R Racaniello
1Department of Microbiology, Columbia University College of Physicians, New York, NY 10032, USA. vrr1@columbia.edu
Enteroviruses, like poliovirus, can overcome the cell's antiviral defenses. The enteroviral 2A proteinase (2Apro) is key to blocking interferon-stimulated gene activity, enabling virus replication.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Picornaviridae viruses cause various diseases.
- Some picornaviruses inhibit the interferon pathway.
- The effect of picornaviruses on post-interferon signaling is unknown.
Purpose of the Study:
- To investigate if enteroviruses can antagonize interferon-stimulated gene (ISG) antiviral activity.
- To identify viral mechanisms involved in overcoming interferon-induced immunity.
Main Methods:
- Cells were pretreated with alpha interferon (IFN-α).
- Cells were infected with various enteroviruses (poliovirus, enterovirus 70, human rhinovirus 16).
- Replication of other viruses (VSV, EMCV) and the role of enteroviral 2A proteinase (2Apro) were assessed.
Main Results:
- Enteroviruses replicated in IFN-α-treated cells, while VSV and EMCV replication was inhibited.
- Coinfection with poliovirus allowed EMCV replication in IFN-α-treated cells.
- Enteroviral 2Apro was essential for replication in IFN-α-treated cells; mutations rendered poliovirus sensitive to IFN-α.
- Introducing poliovirus 2Apro into EMCV enabled its replication in IFN-α-treated cells.
Conclusions:
- Enteroviruses antagonize the antiviral state induced by interferon.
- The enteroviral 2Apro proteinase plays a critical role in inhibiting the downstream antiviral activities of interferon-stimulated genes.
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