Coronavirus and PARP expression dysregulate the NAD Metabolome: a potentially actionable component of innate immunity.

BioRxiv : the Preprint Server for Biology
C. D. HeerCharles Brenner

Abstract

SARS-CoV-2 is a coronavirus (CoV) and cause of COVID-19, which is much more lethal in older people and those with comorbid conditions for unknown reasons. Innate immune responses to CoVs are initiated by recognition of double-stranded RNA and induction of interferon, which turns on a gene expression program that inhibits viral replication. Here we show that SARS-CoV-2 infection of cells, ferrets and a person strikingly dysregulates the NAD gene set by inducing a set of PARP family members that includes enzymes required for the innate immune response to CoVs. CoV infection also induces a severe attack on host cell NAD. Overexpression of one induced enzyme, PARP10, is sufficient to depress host NAD. Gene expression and pharmacological data suggest that boosting NAD through the nicotinamide and nicotinamide riboside kinase pathways may restore antiviral PARP functions to support innate immunity to CoVs, whereas PARP1,2 inhibition does not restore PARP10 activity.

Citations

Aug 9, 2020·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Santosh Shenoy
Sep 24, 2020·Critical Reviews in Biochemistry and Molecular Biology·Daniel J Sanderson, Michael S Cohen
May 30, 2020·Aging·Amber L MuellerDavid A Sinclair
Jan 12, 2021·Journal of Proteome Research·Shalini AggarwalSanjeeva Srivastava
Jan 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Robert G HammondMargaret A Johnson
Dec 22, 2020·Frontiers in Physiology·Aleksei G Golubev
May 8, 2021·Wellcome Open Research·Karl J FristonChristian Lambert

Datasets Mentioned

BETA
GSE147507

Methods Mentioned

BETA
biopsy
bronchoalveolar lavage
RNAseq
RNA-seq
Transfection
chemical treatments
restriction digest

Related Concepts

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.