The coronavirus nucleocapsid protein is ADP-ribosylated

Grunewald, Matthew; Fehr, Anthony R.; Athmer, Jeremiah; Perlman, Stanley

doi:10.1016/j.virol.2017.11.020

Cited by 67 publications

(67 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, alternative functions for the ADRP domain [9][10][11], and its potential targets [12], have been proposed. For example, Fehr et al believe that the domain may act as a de-MAR/PARylating enzyme [9].…”

mentioning

confidence: 99%

The ADRP domain from a virulent strain of infectious bronchitis virus is not sufficient to confer a pathogenic phenotype to the attenuated Beaudette strain

Keep

Bickerton

Armesto

et al. 2018

Journal of General Virology

View full text Add to dashboard Cite

The replicase gene of the coronavirus infectious bronchitis virus (IBV) encodes 15 non-structural proteins (nsps). Nsp 3 is a multi-functional protein containing a conserved ADP-ribose-1″-phosphatase (ADRP) domain. The crystal structures of the domain from two strains of IBV, M41 (virulent) and Beaudette (avirulent), identified a key difference; M41 contains a conserved triple-glycine motif, whilst Beaudette contains a glycine-to-serine mutation that is predicted to abolish ADRP activity. Although ADRP activity has not been formally demonstrated for IBV nsp 3, Beaudette fails to bind ADP-ribose. The role of ADRP in virulence was investigated by generating rIBVs, based on Beaudette, containing either a restored triple-glycine motif or the complete M41 ADRP domain. Replication in vitro was unaffected by the ADRP modifications and the in vivo phenotype of the rIBVs was found to be apathogenic, indicating that restoration of the triple-glycine motif is not sufficient to restore virulence to the apathogenic Beaudette strain.

show abstract

mentioning

confidence: 99%

The ADRP domain from a virulent strain of infectious bronchitis virus is not sufficient to confer a pathogenic phenotype to the attenuated Beaudette strain

Keep

Bickerton

Armesto

et al. 2018

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…The nucleocapsid protein of porcine reproductive and respiratory syndrome virus (PRRSV) binds to PARP1, and the interaction is critical for viral replication, since the use of a PARP inhibitor led to inhibited viral growth (156). In an intriguing parallel, Grunewald et al have shown that the nucleocapsid proteins of both ␣and ␤-coronaviruses are MARylated during infection (157). The function of this modification, and whether it is pro-or antiviral, is currently unknown.…”

Section: Parps In Proviral Responsesmentioning

confidence: 99%

“…It has been suggested that macrodomain activity may antagonize the antiviral effects of ADP-ribosylation (157). Most macrodomains possess conserved primary sequences, but some subclasses lack sequence conservation, resulting in novel functions.…”

Section: Marylation and Its Reversalmentioning

confidence: 99%

Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity

Brady

Goel

Johnson

2019

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

SUMMARYThe literature review presented here details recent research involving members of the poly(ADP-ribose) polymerase (PARP) family of proteins. Among the 17 recognized members of the family, the human enzyme PARP1 is the most extensively studied, resulting in a number of known biological and metabolic roles. This review is focused on the roles played by PARP enzymes in host-pathogen interactions and in diseases with an associated inflammatory response. In mammalian cells, several PARPs have specific roles in the antiviral response; this is perhaps best illustrated by PARP13, also termed the zinc finger antiviral protein (ZAP). Plant stress responses and immunity are also regulated by poly(ADP-ribosyl)ation. PARPs promote inflammatory responses by stimulating proinflammatory signal transduction pathways that lead to the expression of cytokines and cell adhesion molecules. Hence, PARP inhibitors show promise in the treatment of inflammatory disorders and conditions with an inflammatory component, such as diabetes, arthritis, and stroke. These functions are correlated with the biophysical characteristics of PARP family enzymes. This work is important in providing a comprehensive understanding of the molecular basis of pathogenesis and host responses, as well as in the identification of inhibitors. This is important because the identification of inhibitors has been shown to be effective in arresting the progression of disease.

show abstract

“…The nucleocapsid structure not only requires the recognition of the characteristic sequences of the viral RNA, but also must recognize binding to other structural viral proteins. After the N protein forms a complex with the viral genomic RNA, the RNA is protected from destruction by nucleases in the host cell [30]. X-ray diffraction measurement at very high resolution (2.4 Å) was used to discover an intrinsically disordered region (IDR) and an NTD at the N-terminus of the N protein.…”

Section: Virion Replication and Assemblymentioning

confidence: 99%

“…In a study that screened for ADP-ribosylating proteins after infection with CoV, researchers identified an ADP-ribosylated protein of about 55 kDa in vivo, which was subsequently verified as a CoV N protein. Therefore, CoV N proteins may modulate the post-translational modification of certain important proteins [30].…”

Section: Post-translational Modificationmentioning

confidence: 99%

Molecular Characteristics, Functions, and Related Pathogenicity of MERS-CoV Proteins

et al. 2019

Engineering

View full text Add to dashboard Cite

a b s t r a c tMiddle East respiratory syndrome (MERS) is a viral respiratory disease caused by a de novo coronavirus-MERS-CoV-that is associated with high mortality. However, the mechanism by which MERS-CoV infects humans remains unclear. To date, there is no effective vaccine or antibody for human immunity and treatment, other than the safety and tolerability of the fully human polyclonal Immunoglobulin G (IgG) antibody (SAB-301) as a putative therapeutic agent specific for MERS. Although rapid diagnostic and public health measures are currently being implemented, new cases of MERS-CoV infection are still being reported. Therefore, various effective measures should be taken to prevent the serious impact of similar epidemics in the future. Further investigation of the epidemiology and pathogenesis of the virus, as well as the development of effective therapeutic and prophylactic anti-MERS-CoV infections, is necessary. For this purpose, detailed information on MERS-CoV proteins is needed. In this review, we describe the major structural and nonstructural proteins of MERS-CoV and summarize different potential strategies for limiting the outbreak of MERS-CoV. The combination of computational biology and virology can accelerate the advanced design and development of effective peptide therapeutics against MERS-CoV. In summary, this review provides important information about the progress of the elimination of MERS, from prevention to treatment.

show abstract

The coronavirus nucleocapsid protein is ADP-ribosylated

Cited by 67 publications

References 52 publications

The ADRP domain from a virulent strain of infectious bronchitis virus is not sufficient to confer a pathogenic phenotype to the attenuated Beaudette strain

The ADRP domain from a virulent strain of infectious bronchitis virus is not sufficient to confer a pathogenic phenotype to the attenuated Beaudette strain

Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity

Molecular Characteristics, Functions, and Related Pathogenicity of MERS-CoV Proteins

Contact Info

Product

Resources

About