Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Coronavirus infection and PARP expression dysregulate the NAD metabolome : An actionable component of innate immunity. / Heer, Collin D.; Sanderson, Daniel J.; Voth, Lynden S.; Alhammad, Yousef M. O.; Schmidt, Mark S.; Trammell, Samuel A. J.; Perlman, Stanley; Cohen, Michael S.; Fehr, Anthony R.; Brenner, Charles.

I: Journal of Biological Chemistry, Bind 295, Nr. 52, 2020, s. 17986-17996.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Heer, CD, Sanderson, DJ, Voth, LS, Alhammad, YMO, Schmidt, MS, Trammell, SAJ, Perlman, S, Cohen, MS, Fehr, AR & Brenner, C 2020, 'Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity', Journal of Biological Chemistry, bind 295, nr. 52, s. 17986-17996. https://doi.org/10.1074/jbc.RA120.015138

APA

Heer, C. D., Sanderson, D. J., Voth, L. S., Alhammad, Y. M. O., Schmidt, M. S., Trammell, S. A. J., Perlman, S., Cohen, M. S., Fehr, A. R., & Brenner, C. (2020). Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity. Journal of Biological Chemistry, 295(52), 17986-17996. https://doi.org/10.1074/jbc.RA120.015138

Vancouver

Heer CD, Sanderson DJ, Voth LS, Alhammad YMO, Schmidt MS, Trammell SAJ o.a. Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity. Journal of Biological Chemistry. 2020;295(52):17986-17996. https://doi.org/10.1074/jbc.RA120.015138

Author

Heer, Collin D. ; Sanderson, Daniel J. ; Voth, Lynden S. ; Alhammad, Yousef M. O. ; Schmidt, Mark S. ; Trammell, Samuel A. J. ; Perlman, Stanley ; Cohen, Michael S. ; Fehr, Anthony R. ; Brenner, Charles. / Coronavirus infection and PARP expression dysregulate the NAD metabolome : An actionable component of innate immunity. I: Journal of Biological Chemistry. 2020 ; Bind 295, Nr. 52. s. 17986-17996.

Bibtex

@article{73660275f60d426794a48bda2c10f500,
title = "Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity",
abstract = "Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD(+) and NADP(+). Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.",
keywords = "Severe acute respiratory syndrome coronavirus 2, transcriptomics, interferon, poly(ADP-ribose) polymerase, ADP-ribosylation, nicotinamide adenine dinucleotide (NAD), NAD biosynthesis, gene transcription, plus-stranded RNA virus, post-translational modification (PTM), PARP, RNA-Seq, SARS-CoV-2, COVID-19, NICOTINAMIDE RIBOSIDE, ADP-RIBOSYLATION, INHIBITORS",
author = "Heer, {Collin D.} and Sanderson, {Daniel J.} and Voth, {Lynden S.} and Alhammad, {Yousef M. O.} and Schmidt, {Mark S.} and Trammell, {Samuel A. J.} and Stanley Perlman and Cohen, {Michael S.} and Fehr, {Anthony R.} and Charles Brenner",
year = "2020",
doi = "10.1074/jbc.RA120.015138",
language = "English",
volume = "295",
pages = "17986--17996",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "52",

}

RIS

TY - JOUR

T1 - Coronavirus infection and PARP expression dysregulate the NAD metabolome

T2 - An actionable component of innate immunity

AU - Heer, Collin D.

AU - Sanderson, Daniel J.

AU - Voth, Lynden S.

AU - Alhammad, Yousef M. O.

AU - Schmidt, Mark S.

AU - Trammell, Samuel A. J.

AU - Perlman, Stanley

AU - Cohen, Michael S.

AU - Fehr, Anthony R.

AU - Brenner, Charles

PY - 2020

Y1 - 2020

N2 - Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD(+) and NADP(+). Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.

AB - Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD(+) and NADP(+). Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.

KW - Severe acute respiratory syndrome coronavirus 2

KW - transcriptomics

KW - interferon

KW - poly(ADP-ribose) polymerase

KW - ADP-ribosylation

KW - nicotinamide adenine dinucleotide (NAD)

KW - NAD biosynthesis

KW - gene transcription

KW - plus-stranded RNA virus

KW - post-translational modification (PTM)

KW - PARP

KW - RNA-Seq

KW - SARS-CoV-2

KW - COVID-19

KW - NICOTINAMIDE RIBOSIDE

KW - ADP-RIBOSYLATION

KW - INHIBITORS

U2 - 10.1074/jbc.RA120.015138

DO - 10.1074/jbc.RA120.015138

M3 - Journal article

C2 - 33051211

VL - 295

SP - 17986

EP - 17996

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 52

ER -

ID: 255461179