Site-specific SUMOylation of viral polymerase processivity factor: a way of localizingtoND10 subnuclear domains for restricted and self-controlled reproduction of herpesvirus

Lytic replication of human cytomegalovirus (HCMV), a member of β-herpesvirus, is a highly complicated and organized process that requires its DNA polymerase processivity factor, UL44, the first reported HCMV replication protein subjected to SUMO post-translational modification (PTM). SUMOylation pla...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shuyan Lai, Mengqiong Xu, Yaohao Wang, Ruilin Li, Chuan Xia, Sisi Xia, Jun Chen
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	human cytomegalovirus (hcmv) viral polymerase processivity factor ul44 e3 sumo ligase pias3 sumoylation sumo conjugation motif (scm) subnuclear localization, nd10 Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/1c90afced70044b380a3ee5eb68fac06
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1c90afced70044b380a3ee5eb68fac06
record_format	dspace
spelling	oai:doaj.org-article:1c90afced70044b380a3ee5eb68fac062021-11-11T14:23:42ZSite-specific SUMOylation of viral polymerase processivity factor: a way of localizingtoND10 subnuclear domains for restricted and self-controlled reproduction of herpesvirus2150-55942150-560810.1080/21505594.2021.2000689https://doaj.org/article/1c90afced70044b380a3ee5eb68fac062021-11-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2021.2000689https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Lytic replication of human cytomegalovirus (HCMV), a member of β-herpesvirus, is a highly complicated and organized process that requires its DNA polymerase processivity factor, UL44, the first reported HCMV replication protein subjected to SUMO post-translational modification (PTM). SUMOylation plays a pleiotropic role in protein functions of host cells and infecting viruses. Particularly, formation of herpesviral replication compartments (RCs) upon infection is induced in proximity to ND10 subnuclear domains, the host cell’s intrinsic antiviral immune devices and hot SUMOylation spots, relying just on SUMOylation of their protein components to become mature and functional in restriction of the viral replication. In this study, to unveil the exact role of SUMO PTM on UL44 involved in HCMV replication, we screened and identified PIAS3, an annotated E3 SUMO ligase, as a novel UL44-interacting protein engaged in cellular SUMOylation pathway. Co-existence of PIAS3 could enhance the UBC9-based SUMO modification of UL44 specifically at its conserved 410lysine residue lying within the single canonical ψKxE SUMO Conjugation Motif (SCM). Intriguingly, we found this SCM-specific SUMOylation contributes to UL44 co-localization and interaction with subnuclear ND10 domains during infection, which in turn exerts an inhibitory effect on HCMV replication and growth. Together, these results highlight the importance of SUMOylation in regulating viral protein subnuclear localization, representing a novel way of utilizing ND10-based restriction to achieve the self-controlled replication and reproduction of herpesviruses. Importance In this study, we found PIAS3 serves as an additional E3 SUMO ligase towards UL44 possessing modification site specificity at canonical SCM, which renders the UL44 SUMOylation system more integral. We reveal how the site-specific SUMOylation mediates the recruitment of viral replication protein onto the host antiviral subnuclear structures, shedding light on virus-host interplay during infection and meanwhile providing insight into antiviral mechanism of ND10 domains. In addition, from the view of viral evolution, the site-specific SUMOylation motif, genetically retained in HCMV replicating protein to exert an ND10-based antiviral effect, might in turn guarantee the virus a self-controlled slower replication progression upon infection, which is beneficial for viral long-term reproduction.Shuyan LaiMengqiong XuYaohao WangRuilin LiChuan XiaSisi XiaJun ChenTaylor & Francis Grouparticlehuman cytomegalovirus (hcmv)viral polymerase processivity factorul44e3 sumo ligasepias3sumoylationsumo conjugation motif (scm)subnuclear localization, nd10Infectious and parasitic diseasesRC109-216ENVirulence, Vol 0, Iss 0 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	human cytomegalovirus (hcmv) viral polymerase processivity factor ul44 e3 sumo ligase pias3 sumoylation sumo conjugation motif (scm) subnuclear localization, nd10 Infectious and parasitic diseases RC109-216
spellingShingle	human cytomegalovirus (hcmv) viral polymerase processivity factor ul44 e3 sumo ligase pias3 sumoylation sumo conjugation motif (scm) subnuclear localization, nd10 Infectious and parasitic diseases RC109-216 Shuyan Lai Mengqiong Xu Yaohao Wang Ruilin Li Chuan Xia Sisi Xia Jun Chen Site-specific SUMOylation of viral polymerase processivity factor: a way of localizingtoND10 subnuclear domains for restricted and self-controlled reproduction of herpesvirus
description	Lytic replication of human cytomegalovirus (HCMV), a member of β-herpesvirus, is a highly complicated and organized process that requires its DNA polymerase processivity factor, UL44, the first reported HCMV replication protein subjected to SUMO post-translational modification (PTM). SUMOylation plays a pleiotropic role in protein functions of host cells and infecting viruses. Particularly, formation of herpesviral replication compartments (RCs) upon infection is induced in proximity to ND10 subnuclear domains, the host cell’s intrinsic antiviral immune devices and hot SUMOylation spots, relying just on SUMOylation of their protein components to become mature and functional in restriction of the viral replication. In this study, to unveil the exact role of SUMO PTM on UL44 involved in HCMV replication, we screened and identified PIAS3, an annotated E3 SUMO ligase, as a novel UL44-interacting protein engaged in cellular SUMOylation pathway. Co-existence of PIAS3 could enhance the UBC9-based SUMO modification of UL44 specifically at its conserved 410lysine residue lying within the single canonical ψKxE SUMO Conjugation Motif (SCM). Intriguingly, we found this SCM-specific SUMOylation contributes to UL44 co-localization and interaction with subnuclear ND10 domains during infection, which in turn exerts an inhibitory effect on HCMV replication and growth. Together, these results highlight the importance of SUMOylation in regulating viral protein subnuclear localization, representing a novel way of utilizing ND10-based restriction to achieve the self-controlled replication and reproduction of herpesviruses. Importance In this study, we found PIAS3 serves as an additional E3 SUMO ligase towards UL44 possessing modification site specificity at canonical SCM, which renders the UL44 SUMOylation system more integral. We reveal how the site-specific SUMOylation mediates the recruitment of viral replication protein onto the host antiviral subnuclear structures, shedding light on virus-host interplay during infection and meanwhile providing insight into antiviral mechanism of ND10 domains. In addition, from the view of viral evolution, the site-specific SUMOylation motif, genetically retained in HCMV replicating protein to exert an ND10-based antiviral effect, might in turn guarantee the virus a self-controlled slower replication progression upon infection, which is beneficial for viral long-term reproduction.
format	article
author	Shuyan Lai Mengqiong Xu Yaohao Wang Ruilin Li Chuan Xia Sisi Xia Jun Chen
author_facet	Shuyan Lai Mengqiong Xu Yaohao Wang Ruilin Li Chuan Xia Sisi Xia Jun Chen
author_sort	Shuyan Lai
title	Site-specific SUMOylation of viral polymerase processivity factor: a way of localizingtoND10 subnuclear domains for restricted and self-controlled reproduction of herpesvirus
title_short	Site-specific SUMOylation of viral polymerase processivity factor: a way of localizingtoND10 subnuclear domains for restricted and self-controlled reproduction of herpesvirus
title_full	Site-specific SUMOylation of viral polymerase processivity factor: a way of localizingtoND10 subnuclear domains for restricted and self-controlled reproduction of herpesvirus
title_fullStr	Site-specific SUMOylation of viral polymerase processivity factor: a way of localizingtoND10 subnuclear domains for restricted and self-controlled reproduction of herpesvirus
title_full_unstemmed	Site-specific SUMOylation of viral polymerase processivity factor: a way of localizingtoND10 subnuclear domains for restricted and self-controlled reproduction of herpesvirus
title_sort	site-specific sumoylation of viral polymerase processivity factor: a way of localizingtond10 subnuclear domains for restricted and self-controlled reproduction of herpesvirus
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/1c90afced70044b380a3ee5eb68fac06
work_keys_str_mv	AT shuyanlai sitespecificsumoylationofviralpolymeraseprocessivityfactorawayoflocalizingtond10subnucleardomainsforrestrictedandselfcontrolledreproductionofherpesvirus AT mengqiongxu sitespecificsumoylationofviralpolymeraseprocessivityfactorawayoflocalizingtond10subnucleardomainsforrestrictedandselfcontrolledreproductionofherpesvirus AT yaohaowang sitespecificsumoylationofviralpolymeraseprocessivityfactorawayoflocalizingtond10subnucleardomainsforrestrictedandselfcontrolledreproductionofherpesvirus AT ruilinli sitespecificsumoylationofviralpolymeraseprocessivityfactorawayoflocalizingtond10subnucleardomainsforrestrictedandselfcontrolledreproductionofherpesvirus AT chuanxia sitespecificsumoylationofviralpolymeraseprocessivityfactorawayoflocalizingtond10subnucleardomainsforrestrictedandselfcontrolledreproductionofherpesvirus AT sisixia sitespecificsumoylationofviralpolymeraseprocessivityfactorawayoflocalizingtond10subnucleardomainsforrestrictedandselfcontrolledreproductionofherpesvirus AT junchen sitespecificsumoylationofviralpolymeraseprocessivityfactorawayoflocalizingtond10subnucleardomainsforrestrictedandselfcontrolledreproductionofherpesvirus
_version_	1718438917759303680

Site-specific SUMOylation of viral polymerase processivity factor: a way of localizingtoND10 subnuclear domains for restricted and self-controlled reproduction of herpesvirus

Ejemplares similares