A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication
Vaccinology Group, Pirbright Laboratories, Institute for Animal Health, Surrey, United Kingdom. Advances in Virus Research
(Impact Factor: 4.57).
02/2007; 70:101-82. DOI: 10.1016/S0065-3527(07)70004-0
Virus replication can cause extensive rearrangement of host cell cytoskeletal and membrane compartments leading to the "cytopathic effect" that has been the hallmark of virus infection in tissue culture for many years. Recent studies are beginning to redefine these signs of viral infection in terms of specific effects of viruses on cellular processes. In this chapter, these concepts have been illustrated by describing the replication sites produced by many different viruses. In many cases, the cellular rearrangements caused during virus infection lead to the construction of sophisticated platforms in the cell that concentrate replicase proteins, virus genomes, and host proteins required for replication, and thereby increase the efficiency of replication. Interestingly, these same structures, called virus factories, virus inclusions, or virosomes, can recruit host components that are associated with cellular defences against infection and cell stress. It is possible that cellular defence pathways can be subverted by viruses to generate sites of replication. The recruitment of cellular membranes and cytoskeleton to generate virus replication sites can also benefit viruses in other ways. Disruption of cellular membranes can, for example, slow the transport of immunomodulatory proteins to the surface of infected cells and protect against innate and acquired immune responses, and rearrangements to cytoskeleton can facilitate virus release.
Available from: Peter D Nagy
- "This pathway is based on conserved FFAT-motif and VAP-containing host proteins. This is beneficial for TBSV since virus replication requires new cellular membranes for replication, similar to many other ( þ)RNA viruses (Castorena et al., 2010; Netherton et al., 2007). "
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ABSTRACT: Positive-stranded RNA viruses induce new membranous structures and promote membrane proliferation in infected cells to facilitate viral replication. In this paper, the authors show that a plant-infecting tombusvirus upregulates transcription of phospholipid biosynthesis genes, such as INO1, OPI3 and CHO1, and increases phospholipid levels in yeast model host. This is accomplished by the viral p33 replication protein, which interacts with Opi1p FFAT domain protein and Scs2p VAP protein. Opi1p and Scs2p are phospholipid sensor proteins and they repress the expression of phospholipid genes. Accordingly, deletion of OPI1 transcription repressor in yeast has a stimulatory effect on TBSV RNA accumulation and enhanced tombusvirus replicase activity in an in vitro assay. Altogether, the presented data convincingly demonstrate that de novo lipid biosynthesis is required for optimal TBSV replication. Overall, this work reveals that a (+)RNA virus reprograms the phospholipid biosynthesis pathway in a unique way to facilitate its replication in yeast cells.
Available from: Miguel Aranda
- "Most eukaryotic (+) single-straded RNA viruses replicate in association with cell membranes. Often, these viruses induce changes such as proliferation or invagination of membranes to create structures that allow assembly of replication proteins (Ahlquist 2006; Fernández de Castro et al. 2013; Laliberté and Sanfaçon 2010; Mine and Okuno 2012; Netherton et al. 2007). "
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ABSTRACT: Melon necrotic spot virus (MNSV; genus Carmovirus, family Tombusviridae) is a single stranded, positive-sense RNA virus that has become an experimental model for the analysis of cell-to-cell virus movement and translation of uncapped viral RNAs whereas little is known about its replication. Analysis of the cytopathology after MNSV infection showed the specific presence of modified organelles that resemble mitochondria. Immunolocalisation of the glycine-decarboxylase P protein in these organelles confirmed their mitochondrial origin. In situ hybridisation and immunolocalization experiments showed the specific localization of positive-sense viral RNA, CP and dsRNA in these organelles meaning that replication of the virus takes place in association with them. The 3D reconstructions of the altered mitochondria showed the presence of large, interconnected, internal dilatations which appeared to be linked to the outside cytoplasmic environment through pores and/or complex structures, and with lipid bodies. Transient expression of MNSV p29 revealed that its specific target is mitochondria. Our data document the extensive reorganization of host mitochondria induced by MNSV, which provides a protected environment to viral replication, and show that the MNSV p29 protein is the primary determinant of this effect in the host.
Available from: Jeanmarie Verchot
- "Serving as a model process in the field of stress biology, positive strand RNA viruses infecting mammals and plants pose an enormous biosynthetic burden on the ER. To aid cellular adaptation to infection, viruses trigger vigorous membrane and protein synthesis, and/or protein transfer to the Golgi apparatus (Netherton et al., 2007). Host gene expression is transiently enhanced to adapt to the immediate needs of virus gene expression, mitigate ER stress, and create a cellular environment that tolerates virus infection. "
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ABSTRACT: The endoplasmic reticulum (ER) is central to protein production and membrane lipid synthesis. The unfolded protein response (UPR) supports cellular metabolism by ensuring protein quality control in the ER. Most positive strand RNA viruses cause extensive remodeling of membranes and require active membrane synthesis to promote infection. How viruses interact with the cellular machinery controlling membrane metabolism is largely unknown. Furthermore, there is mounting data pointing to the importance of the UPR and ER associated degradation (ERAD) machineries in viral pathogenesis in eukaryotes emerging topic. For many viruses, the UPR is an early event that is essential for persistent infection and benefits virus replication. In addition, many viruses are reported to commandeer ER resident chaperones to contribute to virus replication and intercellular movement. In particular, calreticulin, the ubiquitin machinery, and the 26S proteasome are most commonly identified components of the UPR and ERAD machinery that also regulate virus infection. In addition, researchers have noted a link between UPR and autophagy. It is well accepted that positive strand RNA viruses use autophagic membranes as scaffolds to support replication and assembly. However this topic has yet to be explored using plant viruses. The goal of research on this topic is to uncover how viruses interact with this ER-related machinery and to use this information for designing novel strategies to boost immune responses to virus infection.
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