PARP14 is an interferon (IFN)-induced host factor that promotes IFN production and affects the replication of

Srivatsan Parthasarathy1, Pradtahna Saenjamsai1, Hongping Hao1

  • 1Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, USA.

Insights

Poly(ADP-ribose) polymerase 14 (PARP14) enhances interferon production and restricts viral replication, exhibiting both pro- and antiviral functions against diverse viruses like coronaviruses and herpes simplex virus 1.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Poly(ADP-ribose) polymerase 14 (PARP14) is known for its roles in DNA damage, inflammation, and cancer.
  • PARP14 is upregulated by interferon (IFN) and implicated in host-pathogen interactions.
  • Previous studies suggested PARP14's involvement in IFN-I production during coronavirus infection but its direct antiviral role was unclear.

Purpose of the Study:

  • To investigate the direct antiviral functions of PARP14.
  • To determine if PARP14's catalytic activity is essential for its antiviral effects.
  • To assess PARP14's impact on a broad range of viruses beyond coronaviruses.

Main Methods:

  • Utilized PARP14 knockout (KO) A549 cells to study viral replication.
  • Infected KO cells with various viruses, including murine hepatitis virus (MHV), SARS-CoV-2, herpes simplex virus 1 (HSV-1), vesicular stomatitis virus (VSV), Ebola virus (EBOV), and Nipah virus (NiV).
  • Administered a PARP14 active site inhibitor to assess the role of catalytic activity.

Main Results:

  • PARP14 catalytic activity enhanced IFN-I and IFN-III responses.
  • PARP14 restricted replication of ARH-deficient MHV and SARS-CoV-2.
  • PARP14 restricted HSV-1 replication, but was critical for efficient infection by VSV, EBOV, and NiV.
  • PARP14's antiviral effects on HSV-1 and EBOV were independent of its catalytic activity.

Conclusions:

  • PARP14 promotes interferon production, contributing to antiviral defense.
  • PARP14 exhibits context-dependent antiviral functions, restricting some viruses while promoting others.
  • PARP14 plays a multifaceted role in the host response to viral infections, impacting multiple virus families.

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