Ultrastructural Characterization of Zika Virus Replication Factories

Cortese, Mirko; Goellner, Sarah; Acosta, Eliana G.; Neufeldt, Christopher J.; Oleksiuk, Olga; Lampe, Marko; Haselmann, Uta; Funaya, Charlotta; Schieber, Nicole L.; Ronchi, Paolo; Schorb, Martin; Pruunsild, Priit; Schwab, Yannick; Chatel‐Chaix, Laurent; Ruggieri, Alessia; Bartenschlager, Ralf

doi:10.1016/j.celrep.2017.02.014

Cited by 281 publications

(393 citation statements)

References 43 publications

(82 reference statements)

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“…The non-structural proteins regulate viral transcription and replication and are required to modulate host antiviral responses. Interestingly, like all studied positive-strand RNA viruses, flaviviruses hijack cytoplasmic membranes in order to build functional sites for protein translation, processing and RNA replication [10–15]. These sites, generally defined as replication compartments (RCs), are required to efficiently coordinate different steps of the viral life cycle and to shield replicating RNA from innate immunity surveillance [16, 17].…”

Section: Introductionmentioning

confidence: 99%

Antagonism of type I interferon by flaviviruses

Miorin

Maestre

Fernández-Sesma

et al. 2017

Biochemical and Biophysical Research Communications

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The prompt and tightly controlled induction of type I interferon is a central event of the immune defense against viral infection. Flaviviruses comprise a large family of arthropod-borne positive-stranded RNA viruses, many of which represent a serious threat to global human health due to their high rates of morbidity and mortality. All flaviviruses studied so far have been shown to counteract the host’s immune response to establish a productive infection and facilitate viral spread. Here, we review the current knowledge on the main strategies that human pathogenic flaviviruses utilize to escape both type I IFN induction and effector pathways. A better understanding of the specific mechanisms by which flaviviruses activate and evade innate immune responses is critical for the development of better therapeutics and vaccines.

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Section: Introductionmentioning

confidence: 99%

Antagonism of type I interferon by flaviviruses

Miorin

Maestre

Fernández-Sesma

et al. 2017

Biochemical and Biophysical Research Communications

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“…For example, although Zika virus uses MTs to replicate, it disrupts MT networks, but this occurs only when replication is complete and the cell is dying (58). As such, observations of MT disruption or reorganization in infected cells should be interpreted carefully and in context.…”

Section: Resultsmentioning

confidence: 99%

“…Flaviviruses also form replication compartments. For example, Zika virus forms endoplasmic reticulum (ER)-membrane invaginations similar to those of its relative, dengue virus, reorganizing MTs into cages around replication compartments (58). HCV replication compartments consist of both large "membranous webs" that exhibit limited motility and smaller compartments that are motile.…”

Section: Cytoplasmic Replication: Specialized Compartments Need Mts Toomentioning

confidence: 99%

Microtubule Regulation and Function during Virus Infection

Naghavi

Walsh

2017

J Virol

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Microtubules (MTs) form a rapidly adaptable network of filaments that radiate throughout the cell. These dynamic arrays facilitate a wide range of cellular processes, including the capture, transport, and spatial organization of cargos and organelles, as well as changes in cell shape, polarity, and motility. Nucleating from MT-organizing centers, including but by no means limited to the centrosome, MTs undergo rapid transitions through phases of growth, pause, and catastrophe, continuously exploring and adapting to the intracellular environment. Subsets of MTs can become stabilized in response to environmental cues, acquiring distinguishing posttranslational modifications and performing discrete functions as specialized tracks for cargo trafficking. The dynamic behavior and organization of the MT array is regulated by MT-associated proteins (MAPs), which include a subset of highly specialized plus-end-tracking proteins (ϩTIPs) that respond to signaling cues to alter MT behavior. As pathogenic cargos, viruses require MTs to transport to and from their intracellular sites of replication. While interactions with and functions for MT motor proteins are well characterized and extensively reviewed for many viruses, this review focuses on MT filaments themselves. Changes in the spatial organization and dynamics of the MT array, mediated by virus-or host-induced changes to MT regulatory proteins, not only play a central role in the intracellular transport of virus particles but also regulate a wider range of processes critical to the outcome of infection.KEYWORDS virus, cytoskeleton, microtubules, nucleation, microtubule-associated proteins, plus-end-tracking proteins T he dense cytosolic environment poses a major barrier to the free movement of macromolecules, making microtubule (MT)-based transport a critical aspect of virus replication. Indeed, almost as soon as these filaments were identified and characterized, virus particles were observed proximal to "microtubuli," with evidence that MTassociated proteins (MAPs) might mediate this association. Chemicals that disrupt MT networks, still commonly used today, were reported to suppress virus infection. Moreover, either infection or expression of viral proteins was observed to alter the organization of these networks, suggesting that MTs not only facilitated infection but were also likely to be actively manipulated by viruses. In subsequent decades an enormous body of work helped unravel how virus particles exploit MT motors to traffic within infected cells, and we direct readers to a recent review of this subject (1). Here, we discuss recent advances in our understanding of how MTs themselves are regulated and function during infection, limiting this minireview to some illustrative examples in each case. TWO ENDS TO THE STORY: THE BASICS OF MT POLARITY AND ORGANIZATIONMTs form through the polymerization of ␣/␤-tubulin heterodimers into polarized filaments that have minus and plus ends (Fig. 1A and B). MTs nucleate through minus-end seeding at MT-organizing cen...

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“…275 Recently, the ultrastructure of DENV and ZIKV replication complexes in human and mosquito cell lines was visualized using electron tomography. 272,276,277 DENV-induced formation of invaginations into the ER lumen creating 80 nM–120 nm spherules that were often connected to the cytosol by a single, small pore. 272,276 Modification of the lipid composition of the ER membrane is required to alter membrane curvature and form vesicle packets, and this is likely mediated by viral NS proteins (see discussion in section 2.5.2).…”

Section: Biochemistry and Molecular Biology Of Flavivirusesmentioning

confidence: 99%

Biochemistry and Molecular Biology of Flaviviruses

et al. 2018

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Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA–protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune responses. Throughout the review, we highlight areas of intense investigation, or a need for it, and potential targets and tools to consider in the important battle against pathogenic flaviviruses.

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Ultrastructural Characterization of Zika Virus Replication Factories

Cited by 281 publications

References 43 publications

Antagonism of type I interferon by flaviviruses

Antagonism of type I interferon by flaviviruses

Microtubule Regulation and Function during Virus Infection

Biochemistry and Molecular Biology of Flaviviruses

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