Journal
CELL REPORTS
Volume 18, Issue 9, Pages 2113-2123Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.02.014
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Funding
- Natural Sciences and Engineering Research Council of Canada [RGPIN-201605584]
- European Molecular Biology Organization (EMBO) [ALTF 466-2016]
- Deutsche Forschungsgemeinschaft [SFB 1129]
- Excellence Cluster Cell Networks at Heidelberg University
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A global concern has emerged with the pandemic spread of Zika virus (ZIKV) infections that can cause severe neurological symptoms in adults and new-borns. 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.
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