Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid

Entry of circovirus into the host cell nucleus is essential for viral replication during the early stage of infection. However, the mechanisms by which nucleolar shuttle proteins are used during viral replication is still not well understood. Here, we report a previously unidentified nucleolar local...

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Autores principales:	Jianwei Zhou, Yadong Dai, Cui Lin, Ying Zhang, Zixuan Feng, Weiren Dong, Yulan Jin, Yan Yan, Jiyong Zhou, Jinyan Gu
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	circovirus viral capsid nucleophosmin-1 nucleolar localization signal nuclear entry Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/41e1a134f6c84f359e08bf6649dd499f
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spelling	oai:doaj.org-article:41e1a134f6c84f359e08bf6649dd499f2021-11-17T14:21:59ZNucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid2150-55942150-560810.1080/21505594.2020.1832366https://doaj.org/article/41e1a134f6c84f359e08bf6649dd499f2020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1832366https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Entry of circovirus into the host cell nucleus is essential for viral replication during the early stage of infection. However, the mechanisms by which nucleolar shuttle proteins are used during viral replication is still not well understood. Here, we report a previously unidentified nucleolar localization signal in circovirus capsid protein (Cap), and that circovirus hijacks the nucleolar phosphoprotein nucleophosmin-1 (NPM1) to facilitate its replication. Colocalization analysis showed that NPM1 translocates from the nucleolus to the nucleoplasm and cytoplasm during viral infection. Coimmunoprecipitation and glutathione S-transferase pull-down assays showed that Cap interacts directly with NPM1. Binding domain mapping showed that the arginine-rich N-terminal motif 1MTYPRRRYRRRRHRPRSHLG20 of Cap, and residue serine-48 of the N-terminal oligomerization domain of NPM1, are essential for the interaction. Virus rescue experiments showed that all arginine to alanine substitution in the N-terminal arginine-rich motif of Cap resulted in diminished viral replication. Knockdown of NPM1 and substitution of serine-48 in NPM1 to glutamic acid also decreased viral replication. In addition, binding assays showed that the arginine-rich motif of Cap is a nucleolar localization signal. Taken together, our findings demonstrate that circovirus protein Cap is a nucleolus-located, and regulates viral replication by directly binding to NPM1.Jianwei ZhouYadong DaiCui LinYing ZhangZixuan FengWeiren DongYulan JinYan YanJiyong ZhouJinyan GuTaylor & Francis Grouparticlecircovirusviral capsidnucleophosmin-1nucleolar localization signalnuclear entryInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 1379-1393 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	circovirus viral capsid nucleophosmin-1 nucleolar localization signal nuclear entry Infectious and parasitic diseases RC109-216
spellingShingle	circovirus viral capsid nucleophosmin-1 nucleolar localization signal nuclear entry Infectious and parasitic diseases RC109-216 Jianwei Zhou Yadong Dai Cui Lin Ying Zhang Zixuan Feng Weiren Dong Yulan Jin Yan Yan Jiyong Zhou Jinyan Gu Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid
description	Entry of circovirus into the host cell nucleus is essential for viral replication during the early stage of infection. However, the mechanisms by which nucleolar shuttle proteins are used during viral replication is still not well understood. Here, we report a previously unidentified nucleolar localization signal in circovirus capsid protein (Cap), and that circovirus hijacks the nucleolar phosphoprotein nucleophosmin-1 (NPM1) to facilitate its replication. Colocalization analysis showed that NPM1 translocates from the nucleolus to the nucleoplasm and cytoplasm during viral infection. Coimmunoprecipitation and glutathione S-transferase pull-down assays showed that Cap interacts directly with NPM1. Binding domain mapping showed that the arginine-rich N-terminal motif 1MTYPRRRYRRRRHRPRSHLG20 of Cap, and residue serine-48 of the N-terminal oligomerization domain of NPM1, are essential for the interaction. Virus rescue experiments showed that all arginine to alanine substitution in the N-terminal arginine-rich motif of Cap resulted in diminished viral replication. Knockdown of NPM1 and substitution of serine-48 in NPM1 to glutamic acid also decreased viral replication. In addition, binding assays showed that the arginine-rich motif of Cap is a nucleolar localization signal. Taken together, our findings demonstrate that circovirus protein Cap is a nucleolus-located, and regulates viral replication by directly binding to NPM1.
format	article
author	Jianwei Zhou Yadong Dai Cui Lin Ying Zhang Zixuan Feng Weiren Dong Yulan Jin Yan Yan Jiyong Zhou Jinyan Gu
author_facet	Jianwei Zhou Yadong Dai Cui Lin Ying Zhang Zixuan Feng Weiren Dong Yulan Jin Yan Yan Jiyong Zhou Jinyan Gu
author_sort	Jianwei Zhou
title	Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid
title_short	Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid
title_full	Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid
title_fullStr	Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid
title_full_unstemmed	Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid
title_sort	nucleolar protein npm1 is essential for circovirus replication by binding to viral capsid
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/41e1a134f6c84f359e08bf6649dd499f
work_keys_str_mv	AT jianweizhou nucleolarproteinnpm1isessentialforcircovirusreplicationbybindingtoviralcapsid AT yadongdai nucleolarproteinnpm1isessentialforcircovirusreplicationbybindingtoviralcapsid AT cuilin nucleolarproteinnpm1isessentialforcircovirusreplicationbybindingtoviralcapsid AT yingzhang nucleolarproteinnpm1isessentialforcircovirusreplicationbybindingtoviralcapsid AT zixuanfeng nucleolarproteinnpm1isessentialforcircovirusreplicationbybindingtoviralcapsid AT weirendong nucleolarproteinnpm1isessentialforcircovirusreplicationbybindingtoviralcapsid AT yulanjin nucleolarproteinnpm1isessentialforcircovirusreplicationbybindingtoviralcapsid AT yanyan nucleolarproteinnpm1isessentialforcircovirusreplicationbybindingtoviralcapsid AT jiyongzhou nucleolarproteinnpm1isessentialforcircovirusreplicationbybindingtoviralcapsid AT jinyangu nucleolarproteinnpm1isessentialforcircovirusreplicationbybindingtoviralcapsid
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Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid

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