Journal article
The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression
PLoS pathogens, Vol.15(5), e1007756
05/2019
DOI: 10.1371/journal.ppat.1007756
PMCID: PMC6521996
PMID: 31095648
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.
Details
- Title: Subtitle
- The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression
- Creators
- Matthew E Grunewald - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, United States of AmericaYating Chen - Department of Molecular Biosciences, University of Texas, Austin, TX, United States of AmericaChad Kuny - Department of Molecular Biosciences, University of Texas, Austin, TX, United States of AmericaTakashi Maejima - Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of AmericaRobert Lease - McDaniel College, Westminster, MD, United States of AmericaDana Ferraris - McDaniel College, Westminster, MD, United States of AmericaMasanori Aikawa - Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of AmericaChristopher S Sullivan - Department of Molecular Biosciences, University of Texas, Austin, TX, United States of AmericaStanley Perlman - University of Iowa, Stead Family Department of PediatricsAnthony R Fehr - Department of Molecular Biosciences, University of Kansas, Lawrence, KS, United States of America
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.15(5), e1007756
- DOI
- 10.1371/journal.ppat.1007756
- PMID
- 31095648
- PMCID
- PMC6521996
- NLM abbreviation
- PLoS Pathog
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Publisher
- United States
- Grant note
- F32 AI113973 / NIAID NIH HHS\r\nK22 AI134993 / NIAID NIH HHS\r\nP20 GM113117 / NIGMS NIH HHS\r\nR01 HL126901 / NHLBI NIH HHS\r\nT32 GM007337 / NIGMS NIH HHS\r\nR01 AI129269 / NIAID NIH HHS\r\nR01 AI091322 / NIAID NIH HHS\r\nP01 AI060699 / NIAID NIH HHS\r\nR01 NS036592 / NINDS NIH HHS\r\nR01 AI123231 / NIAID NIH HHS
- Language
- English
- Date published
- 05/2019
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9983782098602771
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