The Coronavirus Nucleocapsid is a Multifunctional Protein

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2014 Aug 9

PMID 25105276

Citations 529

Authors

Ruth McBride

Marjorie Van Zyl

Burtram C Fielding

Affiliations

Soon will be listed here.

Abstract

The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. Recent studies have confirmed that N is a multifunctional protein. The aim of this review is to highlight the properties and functions of the N protein, with specific reference to (i) the topology; (ii) the intracellular localization and (iii) the functions of the protein.

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References

Surjit M, Lal S . The SARS-CoV nucleocapsid protein: a protein with multifarious activities. Infect Genet Evol. 2007; 8(4):397-405. PMC: 7106238. DOI: 10.1016/j.meegid.2007.07.004. View

Baudoux P, Carrat C, Besnardeau L, Charley B, Laude H . Coronavirus pseudoparticles formed with recombinant M and E proteins induce alpha interferon synthesis by leukocytes. J Virol. 1998; 72(11):8636-43. PMC: 110275. DOI: 10.1128/JVI.72.11.8636-8643.1998. View

Brierley I, Boursnell M, Binns M, Bilimoria B, Blok V, Brown T . An efficient ribosomal frame-shifting signal in the polymerase-encoding region of the coronavirus IBV. EMBO J. 1987; 6(12):3779-85. PMC: 553849. View

Fang S, Shen H, Wang J, Tay F, Liu D . Proteolytic processing of polyproteins 1a and 1ab between non-structural proteins 10 and 11/12 of Coronavirus infectious bronchitis virus is dispensable for viral replication in cultured cells. Virology. 2008; 379(2):175-80. PMC: 7103401. DOI: 10.1016/j.virol.2008.06.038. View

Menendez A, Chow K, Pan O, Scott J . Human immunodeficiency virus type 1-neutralizing monoclonal antibody 2F5 is multispecific for sequences flanking the DKW core epitope. J Mol Biol. 2004; 338(2):311-27. DOI: 10.1016/j.jmb.2004.02.051. View

Kurasawa Y, Watanabe Y, Numata O . Characterization of F-actin bundling activity of Tetrahymena elongation factor 1 alpha investigated with rabbit skeletal muscle actin. Zoolog Sci. 1996; 13(3):371-5. DOI: 10.2108/zsj.13.371. View

Woo K, Joo M, Narayanan K, Kim K, Makino S . Murine coronavirus packaging signal confers packaging to nonviral RNA. J Virol. 1997; 71(1):824-7. PMC: 191125. DOI: 10.1128/JVI.71.1.824-827.1997. View

Lopez S, Yao J, Kuhn R, Strauss E, Strauss J . Nucleocapsid-glycoprotein interactions required for assembly of alphaviruses. J Virol. 1994; 68(3):1316-23. PMC: 236585. DOI: 10.1128/JVI.68.3.1316-1323.1994. View

Lai M, Cavanagh D . The molecular biology of coronaviruses. Adv Virus Res. 1997; 48:1-100. PMC: 7130985. View

10.

Zuniga S, Sola I, Alonso S, Enjuanes L . Sequence motifs involved in the regulation of discontinuous coronavirus subgenomic RNA synthesis. J Virol. 2003; 78(2):980-94. PMC: 368802. DOI: 10.1128/jvi.78.2.980-994.2004. View

11.

Ruch T, Machamer C . The coronavirus E protein: assembly and beyond. Viruses. 2012; 4(3):363-82. PMC: 3347032. DOI: 10.3390/v4030363. View

12.

Wu C, Yeh S, Tsay Y, Shieh Y, Kao C, Chen Y . Glycogen synthase kinase-3 regulates the phosphorylation of severe acute respiratory syndrome coronavirus nucleocapsid protein and viral replication. J Biol Chem. 2008; 284(8):5229-39. PMC: 8011290. DOI: 10.1074/jbc.M805747200. View

13.

Verheije M, Hagemeijer M, Ulasli M, Reggiori F, Rottier P, Masters P . The coronavirus nucleocapsid protein is dynamically associated with the replication-transcription complexes. J Virol. 2010; 84(21):11575-9. PMC: 2953146. DOI: 10.1128/JVI.00569-10. View

14.

Valegard K, Murray J, Stockley P, Stonehouse N, Liljas L . Crystal structure of an RNA bacteriophage coat protein-operator complex. Nature. 1994; 371(6498):623-6. DOI: 10.1038/371623a0. View

15.

Lomonte P, Everett R . Herpes simplex virus type 1 immediate-early protein Vmw110 inhibits progression of cells through mitosis and from G(1) into S phase of the cell cycle. J Virol. 1999; 73(11):9456-67. PMC: 112980. DOI: 10.1128/JVI.73.11.9456-9467.1999. View

16.

Monaghan A, Webster A, Hay R . Adenovirus DNA binding protein: helix destabilising properties. Nucleic Acids Res. 1994; 22(5):742-8. PMC: 307877. DOI: 10.1093/nar/22.5.742. View

17.

Dalton K, Casais R, Shaw K, Stirrups K, Evans S, Britton P . cis-acting sequences required for coronavirus infectious bronchitis virus defective-RNA replication and packaging. J Virol. 2000; 75(1):125-33. PMC: 113905. DOI: 10.1128/JVI.75.1.125-133.2001. View

18.

Narayanan K, Kim K, Makino S . Characterization of N protein self-association in coronavirus ribonucleoprotein complexes. Virus Res. 2003; 98(2):131-40. PMC: 7125804. DOI: 10.1016/j.virusres.2003.08.021. View

19.

Snijder E, Bredenbeek P, Dobbe J, Thiel V, Ziebuhr J, Poon L . Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J Mol Biol. 2003; 331(5):991-1004. PMC: 7159028. DOI: 10.1016/s0022-2836(03)00865-9. View

20.

Gross S, Kinzy T . Translation elongation factor 1A is essential for regulation of the actin cytoskeleton and cell morphology. Nat Struct Mol Biol. 2005; 12(9):772-8. DOI: 10.1038/nsmb979. View