A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication

Netherton, Christopher L.; Moffat, Katy; Brooks, Elizabeth D.; Wileman, Thomas

doi:10.1016/s0065-3527(07)70004-0

Cited by 200 publications

(172 citation statements)

References 418 publications

(539 reference statements)

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“…Nevertheless, a cytoplasmic cycle raises intriguing questions, because the nucleus provides an optimal, ready-made site for viral replication (1). Thus, an exclusive cytoplasmic infection necessitates de novo generation of a platform that confers the machinery, ingredients, and most significantly, elaborate architecture required for replication of large DNA viruses (26,27). The recently highlighted structural complexity of vaccinia cytoplasmic factories (22) renders the spatiotemporal features that characterize the factory of the larger and more complex Mimivirus into a particularly attractive case study in self-assembly.…”

Section: Discussionmentioning

confidence: 99%

Vaccinia-like cytoplasmic replication of the giant Mimivirus

Mutsafi¹,

Zauberman²,

Sabanay

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

115

127

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Poxviruses are considered to be unique among all DNA viruses, because their infection cycle is carried out exclusively in the host cytoplasm. Such an infection strategy is of interest, because it necessitates generation of elaborate factories in which viral replication and assembly are promoted. By using diverse imaging techniques, we show that the infection cycle of the largest virus currently identified, the Acanthamoeba polyphaga Mimivirus, similarly occurs exclusively in the host cytoplasm. We further show that newly synthesized mRNAs accumulate at discrete cytoplasmic sites that are distinct from the sites where viral replication occurs, and this is observed in vaccinia infection. By revealing substantial physiologic similarity between poxviruses and Mimivirus and thus, implying that an entirely cytoplasmic viral replication might be more common than generally considered, these findings underscore the ability of DNA viruses to generate large and elaborate replication factories.electron tomography | nucleocytoplasmic large DNA viruses | poxviruses | viral factories W ith the single exception of poxviruses, all currently known DNA viruses carry out replication and transcription either entirely or partially within host nuclei. The overwhelming bias to nucleus-centered viral transactions is rationalized by the fact that the nucleus provides the elaborate machinery required for these processes. Moreover, by concentrating essential factors into particular intranuclear sites as well as by enabling spatiotemporal regulation of viral replication and transcription, the nuclear environment considerably enhances the efficiency of these processes (1). Such underlying benefits render the entirely cytoplasmic infection cycle of poxviruses all of the more intriguing (2, 3). Nucleus-centered viral transactions present, however, remarkable hurdles associated with the prerequisite of transporting viral genomes from their entry sites at the cell periphery to and into the nucleus. Specifically, the cellular milieu is refractory to motion of DNA molecules because of the high viscosity of the cytosol and the dense molecular sieve generated by the cytoskeleton (4). Moreover, the nuclear envelope imposes a severe barrier for both entry and exit of long DNA molecules (1).The hurdles associated with genome trafficking are particularly high for nucleocytoplasmic large DNA viruses (NCLDV), which include the eukaryote-infecting families Poxviridae, Phycodnaviridae, Iridoviridae, and Asfarviridae, all characterized by DNA genomes longer than 100 kbp (5). After entry, genomes of phycodnaviruses (6), iridoviruses (7), and the African swine fever virus (8) are released into the cytoplasm at the host cell periphery and then, are shuttled toward and transported into the nucleus where initial replication cycles occur. Viral DNA is subsequently delivered to specific cytoplasmic factories in which all transactions required for viral assembly take place. The factors that attenuate the barriers imposed by the constrained DNA motion and thus, enabl...

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Section: Discussionmentioning

confidence: 99%

Vaccinia-like cytoplasmic replication of the giant Mimivirus

Mutsafi¹,

Zauberman²,

Sabanay

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

115

127

View full text Add to dashboard Cite

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“…In contrast to cytoplasmic replicating viruses, which assemble progeny particles in close association with cellular membranes, virions of DNA viruses replicating in the nucleus are often assembled in close proximity to viral transcription and DNA replication centers devoid of a surrounding membrane (1,5).…”

Section: Nuclear Dna Virus Replication Centersmentioning

confidence: 99%

“…In the case of positive-strand RNA genomes of a variety of virus families, RNA replication is associated with extensive reorganization and generation of single or double membranous structures coopted by membrane-associated viral replicase complexes (RCs). RCs formed by RNA (ϩ) viruses have been the subject of intense investigation, and it is for these virus families that more information is available and has been included in several excellent reviews (1)(2)(3)(4)(5). RNA and DNA viruses that replicate in the cytoplasm form viral factories or viroplasms that require relocalization of organelles, reorganization of the endoplasmic reticulum (ER), Golgi apparatus, endosome, lysosome, mitochondria, or other cellular membranes, and changes in the distribution and dynamics of the cytoskeleton (1)(2)(3)(4)(5).…”

mentioning

confidence: 99%

DNA Virus Replication Compartments

Schmid

Speiseder

Dobner

et al. 2014

J Virol

158

142

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bViruses employ a variety of strategies to usurp and control cellular activities through the orchestrated recruitment of macromolecules to specific cytoplasmic or nuclear compartments. Formation of such specialized virus-induced cellular microenvironments, which have been termed viroplasms, virus factories, or virus replication centers, complexes, or compartments, depends on molecular interactions between viral and cellular factors that participate in viral genome expression and replication and are in some cases associated with sites of virion assembly. These virus-induced compartments function not only to recruit and concentrate factors required for essential steps of the viral replication cycle but also to control the cellular mechanisms of antiviral defense. In this review, we summarize characteristic features of viral replication compartments from different virus families and discuss similarities in the viral and cellular activities that are associated with their assembly and the functions they facilitate for viral replication.

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“…These compartments, which are held together by protein-protein interactions, are thought to concentrate those viral components required to increase the overall efficiency of the replication process (22,23). Factories made by cytoplasmic viruses are large inclusions that usually form at pericentriolar sites close to the microtubule-organizing center (MTOC) and resemble in many ways the aggresomes formed in cells in response to protein misfolding/aggregation (14,32,33).…”

mentioning

confidence: 99%

Avian Reovirus μNS Protein Forms Homo-Oligomeric Inclusions in a Microtubule-Independent Fashion, Which Involves Specific Regions of Its C-Terminal Domain

Brandariz-Núñez

Menaya-Vargas

Benavente

et al. 2010

J Virol

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Members of the genus Orthoreovirus replicate in cytoplasmic inclusions termed viral factories. Compelling evidence suggests that the nonstructural protein NS forms the matrix of the factories and recruits specific viral proteins to these structures. In the first part of this study, we analyzed the properties of avian reovirus factories and NS-derived inclusions and found that they are nonaggresome cytoplasmic globular structures not associated with the cytoskeleton which do not require an intact microtubule network for formation and maturation. We next investigated the capacity of avian reovirus NS to form inclusions in transfected and baculovirus-infected cells. Our results showed that NS is the main component of the inclusions formed by recombinant baculovirus expression. This, and the fact that NS is able to self-associate inside the cell, suggests that NS monomers contain all the interacting domains required for inclusion formation. Examination of the inclusion-forming capacities of truncated NS versions allowed us to identify the region spanning residues 448 to 635 of NS as the smallest that was inclusion competent, although residues within the region 140 to 380 seem to be involved in inclusion maturation. Finally, we investigated the roles that four different motifs present in NS(448-635) play in inclusion formation, and the results suggest that the C-terminal tail domain is a key determinant in dictating the initial orientation of monomer-to-monomer contacts to form basal oligomers that control inclusion shape and inclusion-forming efficiency. Our results contribute to an understanding of the generation of structured protein aggregates that escape the cellular mechanisms of protein recycling.Most viruses replicate within cellular compartments that are termed viroplasms, viral factories, or virus inclusion bodies. These compartments, which are held together by protein-protein interactions, are thought to concentrate those viral components required to increase the overall efficiency of the replication process (22,23). Factories made by cytoplasmic viruses are large inclusions that usually form at pericentriolar sites close to the microtubule-organizing center (MTOC) and resemble in many ways the aggresomes formed in cells in response to protein misfolding/aggregation (14,32,33). Misfolded/aggregated proteins initially form small globular structures that are delivered to the MTOC by dynein-mediated retrograde transport along microtubules for subsequent degradation by proteasomes. When the degradative capacity of the proteasome is exceeded, these aggregates coalesce to form aggresomes, which require microtubules in order to form but not to be maintained. These phase-dense structures located in the perinuclear region are often ubiquitinated, contain dynein, and are surrounded by a vimentin cage to facilitate their positioning near the MTOC.Avian reoviruses (ARVs) are members of the genus Orthoreovirus, one of the 12 genera of the family Reoviridae (1, 20). These viruses have been described as the etiological a...

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A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication

Cited by 200 publications

References 418 publications

Vaccinia-like cytoplasmic replication of the giant Mimivirus

Vaccinia-like cytoplasmic replication of the giant Mimivirus

DNA Virus Replication Compartments

Avian Reovirus μNS Protein Forms Homo-Oligomeric Inclusions in a Microtubule-Independent Fashion, Which Involves Specific Regions of Its C-Terminal Domain

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