Linear ubiquitination regulates the KSHV replication and transcription activator protein to control infection.

Herpesvirus 8, Human / physiology Ubiquitination Humans Virus Replication Immediate-Early Proteins / metabolism HEK293 Cells Trans-Activators / metabolism Ubiquitin-Protein Ligases / metabolism Virus Activation Herpesviridae Infections / metabolism Cell Nucleus / metabolism

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
29 Jun 2024
Historique:
received: 19 11 2023
accepted: 21 06 2024
medline: 2 7 2024
pubmed: 2 7 2024
entrez: 1 7 2024
Statut: epublish

Résumé

Like many other viruses, KSHV has two life cycle modes: the latent phase and the lytic phase. The RTA protein from KSHV is essential for lytic reactivation, but how this protein's activity is regulated is not fully understood. Here, we report that linear ubiquitination regulates the activity of RTA during KSHV lytic reactivation and de novo infection. Overexpressing OTULIN inhibits KSHV lytic reactivation, whereas knocking down OTULIN or overexpressing HOIP enhances it. Intriguingly, we found that RTA is linearly polyubiquitinated by HOIP at K516 and K518, and these modifications control the RTA's nuclear localization. OTULIN removes linear polyubiquitin chains from cytoplasmic RTA, preventing its nuclear import. The RTA orthologs encoded by the EB and MHV68 viruses are also linearly polyubiquitinated and regulated by OTULIN. Our study establishes that linear polyubiquitination plays a critically regulatory role in herpesvirus infection, adding virus infection to the list of biological processes known to be controlled by linear polyubiquitination.

Identifiants

DOI: 10.1038/s41467-024-49887-6 PMID: 38951495
pubmed: 38951495
doi: 10.1038/s41467-024-49887-6
pii: 10.1038/s41467-024-49887-6
doi:

Substances chimiques

Immediate-Early Proteins 0
Trans-Activators 0
Rta protein, Human herpesvirus 8 0
Ubiquitin-Protein Ligases EC 2.3.2.27
RNF31 protein, human EC 2.3.2.27

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

5515

Subventions

Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 31970158
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 31571445

Informations de copyright

© 2024. The Author(s).

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Auteurs

Yi Luan (Y)

Clinical Systems Biology Laboratories, Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Institute of Infection and Immunity, Henan Academy of Innovations in Medical Science, Zhengzhou, China.
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
ORCID: 0000-0002-2511-0359

Wenying Long (W)

Center for Clinical Research, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang, China.

Lisi Dai (L)

Department of Pathology & Pathophysiology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Surgical Oncology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
School of Basic Medical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.

Panfeng Tao (P)

Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China.

Zhifen Deng (Z)

Clinical Systems Biology Laboratories, Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Institute of Infection and Immunity, Henan Academy of Innovations in Medical Science, Zhengzhou, China.
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Zongping Xia (Z)

Clinical Systems Biology Laboratories, Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. zxia2018@zzu.edu.cn.
Institute of Infection and Immunity, Henan Academy of Innovations in Medical Science, Zhengzhou, China. zxia2018@zzu.edu.cn.
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. zxia2018@zzu.edu.cn.
NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. zxia2018@zzu.edu.cn.
ORCID: 0000-0002-1933-4911

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Classifications MeSH

questionsmedicales.fr › Virus › Virus oncogènes › Virus tumoraux à ADN › Gammaherpesvirinae › Rhadinovirus › Herpèsvirus humain de type 8 › Linear ubiquitination regulates the KSHV...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Modification traductionnelle des protéines › Maturation post-traductionnelle des protéines › Ubiquitination › Linear ubiquitination regulates the KSHV...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Linear ubiquitination regulates the KSHV...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › Linear ubiquitination regulates the KSHV...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales régulatrices ou accessoires › Protéines précoces immédiates › Linear ubiquitination regulates the KSHV...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Linear ubiquitination regulates the KSHV...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales régulatrices ou accessoires › Transactivateurs › Linear ubiquitination regulates the KSHV...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › Linear ubiquitination regulates the KSHV...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › Activation virale › Linear ubiquitination regulates the KSHV...
questionsmedicales.fr › Infection › Maladies virales › Infections à virus à ADN › Infections à Herpesviridae › Linear ubiquitination regulates the KSHV...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Noyau de la cellule › Linear ubiquitination regulates the KSHV...