Localization to the Nucleolus Is a Common Feature of Coronavirus Nucleoproteins, and the Protein May Disrupt Host Cell Division

doi:10.1128/JVI.75.19.9345-9356.2001

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Journal of Virology, October 2001, p. 9345-9356, Vol. 75, No. 19
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.19.9345-9356.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Localization to the Nucleolus Is a Common Feature of Coronavirus Nucleoproteins, and the Protein May Disrupt Host Cell Division

Torsten Wurm,¹ Hongying Chen,¹ Teri Hodgson,¹ Paul Britton,² Gavin Brooks,³ and Julian A. Hiscox¹^,^*

Virology Group¹ and Cardiovascular Cell Cycle Control Group,³ School of Animal and Microbial Sciences, University of Reading, Reading, Berkshire RG6 6AJ, and Division of Molecular Biology, Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berkshire RG20 7NN,² United Kingdom

Received 14 March 2001/Accepted 22 June 2001

The subcellular localization of transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) (group I and groupII coronaviruses, respectively) nucleoproteins (N proteins) wereexamined by confocal microscopy. The proteins were shown to localizeeither to the cytoplasm alone or to the cytoplasm and a structurein the nucleus. This feature was confirmed to be the nucleolusby using specific antibodies to nucleolin, a major component ofthe nucleolus, and by confocal microscopy to image sections througha cell expressing N protein. These findings are consistent withour previous report for infectious bronchitis virus (group IIIcoronavirus) (J. A. Hiscox et al., J. Virol. 75:506-512, 2001),indicating that nucleolar localization of the N protein is a commonfeature of the coronavirus family and is possibly of functionalsignificance. Nucleolar localization signals were identified inthe domain III region of the N protein from all three coronavirusgroups, and this suggested that transport of N protein to thenucleus might be an active process. In addition, our results suggestthat the N protein might function to disrupt cell division. Thus,we observed that approximately 30% of cells transfected with theN protein appeared to be undergoing cell division. The most likelyexplanation for this is that the N protein induced a cell cycledelay or arrest, most likely in the G₂/M phase. In a fractionof transfected cells expressing coronavirus N proteins, we observedmultinucleate cells and dividing cells with nucleoli (which areonly present during interphase). These findings are consistentwith the possible inhibition of cytokinesis in thesecells.

^* Corresponding author. Mailing address: School of Animal and Microbial Sciences, University of Reading, Whiteknights, P.O.Box 228, Reading RG6 6AJ, England, United Kingdom. Phone: 44 (0)118931 8893. Fax: 44 (0)118 931 0180. E-mail: j.a.hiscox{at}reading.ac.uk.

Journal of Virology, October 2001, p. 9345-9356, Vol. 75, No. 19
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.19.9345-9356.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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