Ultrastructural Characterization of Zika Virus Replication Factories

A global concern has emerged with the pandemic spread of Zika virus (ZIKV) infections that can cause severe neurological symptoms in adults and newborns. ZIKV is a positive-strand RNA virus replicating in virus-induced membranous replication factories (RFs). Here we used various imaging techniques t...

Full description

Saved in:

Bibliographic Details
Published in:	Cell reports (Cambridge) 2017-02, Vol.18 (9), p.2113-2123
Main Authors:	Cortese, Mirko, Goellner, Sarah, Acosta, Eliana Gisela, Neufeldt, Christopher John, Oleksiuk, Olga, Lampe, Marko, Haselmann, Uta, Funaya, Charlotta, Schieber, Nicole, Ronchi, Paolo, Schorb, Martin, Pruunsild, Priit, Schwab, Yannick, Chatel-Chaix, Laurent, Ruggieri, Alessia, Bartenschlager, Ralf
Format:	Article
Language:	eng
Subjects:	Animals Cell Line Cercopithecus aethiops electron microscopy electron tomography Endoplasmic Reticulum - ultrastructure Endoplasmic Reticulum - virology flavivirus HEK293 Cells Hepatocytes - ultrastructure Hepatocytes - virology Host-Pathogen Interactions - physiology human neural progenitor cells Humans intermediate filaments Intermediate Filaments - metabolism Intermediate Filaments - ultrastructure Life Sciences live-cell imaging microtubules Microtubules - metabolism Microtubules - ultrastructure Neural Stem Cells - ultrastructure Neural Stem Cells - virology replication factories replication organelles Stem Cells - ultrastructure Stem Cells - virology Vero Cells Virus Replication - physiology Zika virus Zika Virus - metabolism Zika Virus - ultrastructure Zika Virus Infection - metabolism Zika Virus Infection - virology
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	A global concern has emerged with the pandemic spread of Zika virus (ZIKV) infections that can cause severe neurological symptoms in adults and newborns. ZIKV is a positive-strand RNA virus replicating in virus-induced membranous replication factories (RFs). Here we used various imaging techniques to investigate the ultrastructural details of ZIKV RFs and their relationship with host cell organelles. Analyses of human hepatic cells and neural progenitor cells infected with ZIKV revealed endoplasmic reticulum (ER) membrane invaginations containing pore-like openings toward the cytosol, reminiscent to RFs in Dengue virus-infected cells. Both the MR766 African strain and the H/PF/2013 Asian strain, the latter linked to neurological diseases, induce RFs of similar architecture. Importantly, ZIKV infection causes a drastic reorganization of microtubules and intermediate filaments forming cage-like structures surrounding the viral RF. Consistently, ZIKV replication is suppressed by cytoskeleton-targeting drugs. Thus, ZIKV RFs are tightly linked to rearrangements of the host cell cytoskeleton. [Display omitted] •ZIKV induces ER membrane invaginations similar to Dengue virus•ZIKV induces profound alterations of the cytoskeleton•Microtubules and intermediate filaments surround the ZIKV replication factory•ZIKV replication is sensitive to cytoskeleton-targeting drugs Cortese et al. show that ZIKV infection in both human hepatoma and neuronal progenitor cells induces drastic structural modification of the cellular architecture. Microtubules and intermediate filaments surround the viral replication factory composed of vesicles corresponding to ER membrane invagination toward the ER lumen. Importantly, alteration of microtubule flexibility impairs ZIKV replication.
ISSN:	2211-1247 2211-1247