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Advances in Virology
Volume 2019, Article ID 8512363, 11 pages
https://doi.org/10.1155/2019/8512363
Research Article

Poly-ADP Ribosyl Polymerase 1 (PARP1) Regulates Influenza A Virus Polymerase

1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
2Department of Biological Sciences, University of Alaska Anchorage, Anchorage, Alaska, USA
3Institute of Virology, University Medical Center Freiburg, 79104 Freiburg, Germany

Correspondence should be addressed to Eric Bortz; ude.aksala@ztrobe

Received 12 November 2018; Revised 16 January 2019; Accepted 11 February 2019; Published 19 March 2019

Academic Editor: Marco Ciotti

Copyright © 2019 Liset Westera et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Influenza A viruses (IAV) are evolutionarily successful pathogens, capable of infecting a number of avian and mammalian species and responsible for pandemic and seasonal epidemic disease in humans. To infect new species, IAV typically must overcome a number of species barriers to entry, replication, and egress, even while virus replication is counteracted by antiviral host factors and innate immune mechanisms. A number of host factors have been found to regulate the replication of IAV by interacting with the viral RNA-dependent RNA polymerase (RdRP). The host factor PARP1, a poly-ADP ribosyl polymerase, was required for optimal functions of human, swine, and avian influenza RdRP in human 293T cells. In IAV infection, PARP1 was required for efficient synthesis of viral nucleoprotein (NP) in human lung A549 cells. Intriguingly, pharmacological inhibition of PARP1 enzymatic activity (PARylation) by 4-amino-1,8-naphthalimide led to a 4-fold increase in RdRP activity, and a 2.3-fold increase in virus titer. Exogenous expression of the natural PARylation inhibitor PARG also enhanced RdRP activity. These data suggest a virus-host interaction dynamic where PARP1 protein itself is required, but cellular PARylation has a distinct suppressive modality, on influenza A viral polymerase activity in human cells.