SAMHD1 phosphorylation and cytoplasmic relocalization after human cytomegalovirus infection limits its antiviral activity

Simone De Meo; Valentina Dell'Oste; Rosa Molfetta; Valentina Tassinari; Lavinia Vittoria Lotti; Simone Vespa; Benedetta Pignoloni; Daniela Angela Covino; Laura Fantuzzi; Roberta Bona; Alessandra Zingoni; Ilaria Nardone; Matteo Biolatti; Alessandra Coscia; Rossella Paolini; Monsef Benkirane; Fredrik Edfors; Tatyana Sandalova; Adnane Achour; John Hiscott; Santo Landolfo; Angela Santoni; Cristina Cerboni

doi:10.1371/journal.ppat.1008855

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SAMHD1 phosphorylation and cytoplasmic relocalization after human cytomegalovirus infection limits its antiviral activity

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SAMHD1 phosphorylation and cytoplasmic relocalization after human cytomegalovirus infection limits its antiviral activity

Simone De Meo, Valentina Dell'Oste, Rosa Molfetta, Valentina Tassinari, Lavinia Vittoria Lotti, Simone Vespa, Benedetta Pignoloni, Daniela Angela Covino, Laura Fantuzzi, Roberta Bona, …

PLoS pathogens, Vol.16(9), p.e1008855

28/09/2020

DOI: https://doi.org/10.1371/journal.ppat.1008855

PMID: 32986788

Résumé

Antiviral Agents - pharmacology

Cyclin-Dependent Kinases - metabolism

Cytomegalovirus - genetics

Cytomegalovirus - pathogenicity

Cytomegalovirus Infections - virology

Cytoplasm - metabolism

Cytoplasm - virology

Herpesviridae Infections - metabolism

Humans

Monomeric GTP-Binding Proteins - metabolism

Phosphorylation

SAM Domain and HD Domain-Containing Protein 1 - genetics

Virus Replication - drug effects

SAMHD1 is a host restriction factor that functions to restrict both retroviruses and DNA viruses, based on its nuclear deoxynucleotide triphosphate (dNTP) hydrolase activity that limits availability of intracellular dNTP pools. In the present study, we demonstrate that SAMHD1 expression was increased following human cytomegalovirus (HCMV) infection, with only a modest effect on infectious virus production. SAMHD1 was rapidly phosphorylated at residue T592 after infection by cellular cyclin-dependent kinases, especially Cdk2, and by the viral kinase pUL97, resulting in a significant fraction of phosho-SAMHD1 being relocalized to the cytoplasm of infected fibroblasts, in association with viral particles and dense bodies. Thus, our findings indicate that HCMV-dependent SAMHD1 cytoplasmic delocalization and inactivation may represent a potential novel mechanism of HCMV evasion from host antiviral restriction activities.

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Détails

Titre: SAMHD1 phosphorylation and cytoplasmic relocalization after human cytomegalovirus infection limits its antiviral activity
Créateurs - sans rôle: Simone De Meo - Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
Valentina Dell'Oste - Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy
Rosa Molfetta - Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
Valentina Tassinari - Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
Lavinia Vittoria Lotti - Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
Simone Vespa - Laboratory of General Pathology, Center of Aging Science and Translational Medicine (CeSI-MeT) and Department of Medical, Oral and Biotechnological Sciences G. d'Annunzio University, Chieti, Italy
Benedetta Pignoloni - Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
Daniela Angela Covino - National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
Laura Fantuzzi - National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
Roberta Bona - National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
Alessandra Zingoni - Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
Ilaria Nardone - Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
Matteo Biolatti - Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy
Alessandra Coscia - Neonatal Unit, Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy
Rossella Paolini - Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
Monsef Benkirane - Université de Montpellier
Fredrik Edfors - Science for Life Laboratory, Department of Medicine Solna, Karolinska Institute, and Division of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
Tatyana Sandalova - Science for Life Laboratory, Department of Medicine Solna, Karolinska Institute, and Division of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
Adnane Achour - Science for Life Laboratory, Department of Medicine Solna, Karolinska Institute, and Division of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
John Hiscott - Istituto Pasteur Italia-Cenci Bolognetti Foundation, Rome, Italy
Santo Landolfo - Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy
Angela Santoni - IRCCS, Neuromed, Pozzilli, Isernia, Italy
Cristina Cerboni - Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
Détails de publication: PLoS pathogens, Vol.16(9), p.e1008855
Identifiants: 99159284709311
Unité académique: Institut de Génétique Humaine - IGH
Langue: English
Type de ressource: Journal article