ER-shaping proteins Atlastins facilitate Zika virus replication

Identification: Monel, Blandine


Description

ER-shaping proteins Atlastins facilitate Zika virus replication
 
Blandine Monel1, Samy Sid-Ahmed1, Cécile Meunier1, Julian Buchrieser1, Sonia Amraoui1, Peng-Peng Zhu2, Julien Burlaud-Gaillard3, Maxime Chazal4, Simon Corroyer-Dumont5, Audrey Salles6, Mohamed-Lamine Hafirassou7, Jacomine Krijnse-Locker5, Philippe Roingeard3, Ali Amara7, Nolwenn Jouvenet4, Craig Blackstone2, Olivier Schwartz1
1Institut Pasteur, Virus and Immunity Unit, Paris, France; 2Cell Biology Section, Neurogenetics Branch, National Institutes of Health, Bethesda, USA; 3Université F. Rabelais et CHRU de Tours, France; 4Institut Pasteur, Viral Genomics and Vaccination Unit, Paris, France; 5Institut Pasteur, Ultra-structural Bio-Imaging (UBI), Paris, France; 6Institut Pasteur, UTechS Photonic BioImaging Citech, Paris, France; 7Laboratoire de Pathologie et Virologie Moléculaire, IUH, Hôpital St. Louis, Paris, France
 
Zika virus (ZIKV) caused major public health concerns during the past decade. As other flaviviruses, ZIKV modifies the Endoplasmic Reticulum (ER) to generate replication factories. We examined the role ER-resident GTPases Atlastins (ATLs), during ZIKV infection. The function of the three isoforms of ATLs is to drive ER membrane fusion. In humans, autosomal mutation of ATLs leads to neurodegenerative disorders. We first silenced expression of ATLs by siRNA or by CRISPR/Cas9 knockout in HeLa cells. In the absence of ATLs, ZIKV replication was significantly decreased. The appearance of cells harboring the viral glycoprotein E, measured by flow cytometry, was slowed down, and the levels of intracellular viral RNA and infectious virus released in the supernatants were reduced. We previously reported that ZIKV triggers a cytopathic effect characterized by the formation of massive ER-derived vacuoles. This vacuolization was no longer visible in cells lacking ATLs. Similar results were observed in primary human dermal fibroblasts. Altogether our data show that ZIKV hijacks ATLs to accelerate viral production. They highlight the role of cellular proteins involved in the dynamic regulation of the shape of the ER during flavivirus replication.
 

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