dc.contributor.author | Grunewald, Matthew E. | |
dc.contributor.author | Chen, Yating | |
dc.contributor.author | Kuny, Chad | |
dc.contributor.author | Maejima, Takashi | |
dc.contributor.author | Lease, Robert | |
dc.contributor.author | Ferraris, Dana | |
dc.contributor.author | Aikawa, Masanori | |
dc.contributor.author | Sullivan, Christopher S. | |
dc.contributor.author | Perlman, Stanley | |
dc.contributor.author | Fehr, Anthony R. | |
dc.date.accessioned | 2022-01-26T15:09:25Z | |
dc.date.available | 2022-01-26T15:09:25Z | |
dc.date.issued | 2019-05-16 | |
dc.identifier.citation | Grunewald ME, Chen Y, Kuny C, Maejima T, Lease R, Ferraris D, et al. (2019) The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression. PLoS Pathog 15(5): e1007756. https://doi.org/10.1371/journal.ppat.1007756 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/32466 | |
dc.description.abstract | ADP-ribosylation is a ubiquitous post-translational addition of either monomers or polymers of ADP-ribose to target proteins by ADP-ribosyltransferases, usually by interferon-inducible diphtheria toxin-like enzymes known as PARPs. While several PARPs have known antiviral activities, these activities are mostly independent of ADP-ribosylation. Consequently, less is known about the antiviral effects of ADP-ribosylation. Several viral families, including Coronaviridae, Togaviridae, and Hepeviridae, encode for macrodomain proteins that bind to and hydrolyze ADP-ribose from proteins and are critical for optimal replication and virulence. These results suggest that macrodomains counter cellular ADP-ribosylation, but whether PARPs or, alternatively, other ADP-ribosyltransferases cause this modification is not clear. Here we show that pan-PARP inhibition enhanced replication and inhibited interferon production in primary macrophages infected with macrodomain-mutant but not wild-type coronavirus. Specifically, knockdown of two abundantly expressed PARPs, PARP12 and PARP14, led to increased replication of mutant but did not significantly affect wild-type virus. PARP14 was also important for the induction of interferon in mouse and human cells, indicating a critical role for this PARP in the regulation of innate immunity. In summary, these data demonstrate that the macrodomain is required to prevent PARP-mediated inhibition of coronavirus replication and enhancement of interferon production. | en_US |
dc.publisher | Public Library of Science | en_US |
dc.rights | © 2019 Grunewald et al. This is an open access article distributed under the terms of the Creative Commons Attribution License. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.title | The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Fehr, Anthony R. | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.1371/journal.ppat.1007756 | en_US |
dc.identifier.orcid | https://orcid.org/ 0000-0002-6199-6273 | en_US |
dc.identifier.orcid | https://orcid.org/ 0000-0003-4213-2354 | en_US |
dc.identifier.orcid | https://orcid.org/ 0000-0003-1560-1573 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess | en_US |