Three-dimensional structure of Rubella virus factories

Fontana, Juan; López‐Iglesias, Carmen; Tzeng, Wen-Ping; Frey, Teryl K.; Fernández, Julio F.; Risco, Cristina

doi:10.1016/j.virol.2010.06.043

“…Viral RNA synthesis occurs on replication complexes, which are membrane bound to a structure called the cytopathic vacuole (CPV). CPVs are of endolysosomal origin and surrounded by rough endoplasmic reticulum (RER) cisternae, the Golgi apparatus, and mitochondria (13,14). CPVs are replication factories and provide a protected environment for virus replication and assembly.…”

mentioning

confidence: 99%

“…However, its precise function and, especially, the underlying molecular mechanisms remain to be determined. The importance of p32 for RV replication and for the association of RV with mitochondria has been indubitably shown (2,13,14,33). In addition, the implication of p32 in apoptotic pathways and in oxidative phosphorylation (oxphos) in some human cancer cells (11, 18) suggests an energy-directed interaction between RV, mitochondria, and p32.…”

mentioning

confidence: 99%

“…In addition, the implication of p32 in apoptotic pathways and in oxidative phosphorylation (oxphos) in some human cancer cells (11,18) suggests an energy-directed interaction between RV, mitochondria, and p32. Moreover, p32 mRNA is increased upon infection with RV (7), and significant amounts of p32 protein were detected in and around CPVs (13). The interaction of RV with mitochondria could result in altered energy metabolism and thus could represent one of the factors contributing to RV teratogenesis.…”

mentioning

confidence: 99%

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Involvement of p32 and Microtubules in Alteration of Mitochondrial Functions by Rubella Virus

Claus

¹

,

Chey

²

,

Sticht

³

et al. 2011

J Virol

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The interaction of the rubella virus (RV) capsid (C) protein and the mitochondrial p32 protein is believed to participate in virus replication. In this study, the physiological significance of the association of RV with mitochondria was investigated by silencing p32 through RNA interference. It was demonstrated that downregulation of p32 interferes with microtubule-directed redistribution of mitochondria in RV-infected cells. However, the association of the viral C protein with mitochondria was not affected. When cell lines either pretreated with respiratory chain inhibitors or cultivated under (mild) hypoxic conditions were infected with RV, viral replication was reduced in a time-dependent fashion. Additionally, RV infection induces increased activity of mitochondrial electron transport chain complex III, which was associated with an increase in the mitochondrial membrane potential. These effects are outstanding among the examples of mitochondrial alterations caused by viruses. In contrast to the preferential localization of p32 to the mitochondrial matrix in most cell lines, RV-permissive cell lines were characterized by an almost exclusive membrane association of p32. Conceivably, this contributes to p32 function(s) during RV replication. The data presented suggest that p32 fulfills an essential function for RV replication in directing trafficking of mitochondria near sites of viral replication to meet the energy demands of the virus.Rubella virus (RV), a single-stranded RNA virus, is the sole member of the genus Rubivirus in the family Togaviridae and causes a generally mild exanthematous childhood disease. However, severe malformations known as congenital rubella syndrome may result from the infection of seronegative women, especially during the first trimester of pregnancy. The mechanisms contributing to RV teratogenesis remain largely unknown. The 5Ј-proximal open reading frame (ORF) of the genome encodes the two replicase proteins P150 and P90, while the 3Ј ORF encodes the structural proteins, the capsid (C) protein and two envelope glycoproteins (E1 and E2). Viral RNA synthesis occurs on replication complexes, which are membrane bound to a structure called the cytopathic vacuole (CPV). CPVs are of endolysosomal origin and surrounded by rough endoplasmic reticulum (RER) cisternae, the Golgi apparatus, and mitochondria (13,14). CPVs are replication factories and provide a protected environment for virus replication and assembly.The C protein of RV represents one of the few RNA virusencoded structural proteins that interact with mitochondria and is so far the only known viral protein that impairs protein transport into mitochondria (17). Additionally, the C protein participates in viral RNA synthesis (42), which is emphasized by its accumulation around CPVs (14). The C protein is also involved in the process of mitochondrial redistribution to a perinuclear region in proximity to CPVs (3,28) and interacts with the p32 protein (3). Besides its predominant localization to the matrix of mitochondria, p32 is a...

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“…Mitochondria often attach to the factory membranous webs and replication organelles. These contacts might mediate the transfer of ATP and specific cell factors (30,31). Viral factories often reach a diameter of several micrometers, and their assembly sometimes involves a major reorganization of the content of the whole cell (15).…”

Section: Entrymentioning

confidence: 99%

“…Spherules that are the replication sites in Flock house virus have been identified in mitochondria and were the first ones studied in 3D by electron tomography (11). Spherules have also been identified in lysosomes where togaviruses nucleate their factory (30,50), in membranes of the secretory pathway used by flaviviruses and bunyaviruses (15,16), in chloroplasts (51), and in peroxisomes (52).…”

Section: Replication Organellesmentioning

confidence: 99%

Three-Dimensional Imaging of Viral Infections

Risco

¹

,

Castro

²

,

Sanz-Sánchez

³

et al. 2014

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Three-dimensional (3D) imaging technologies are beginning to have significant impact in the field of virology, as they are helping us understand how viruses take control of cells. In this article we review several methodologies for 3D imaging of cells and show how these technologies are contributing to the study of viral infections and the characterization of specialized structures formed in virus-infected cells. We include 3D reconstruction by transmission electron microscopy (TEM) using serial sections, electron tomography, and focused ion beam scanning electron microscopy (FIB-SEM). We summarize from these methods selected contributions to our understanding of viral entry, replication, morphogenesis, egress and propagation, and changes in the spatial architecture of virus-infected cells. In combination with live-cell imaging, correlative microscopy, and new techniques for molecular mapping in situ, the availability of these methods for 3D imaging is expected to provide deeper insights into understanding the structural and dynamic aspects of viral infection.

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Rubella Virus

Frey

¹

,

Matthews

²

2011

Encyclopedia of Life Sciences

0

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Rubella virus is a human virus belonging to the family Togaviridae and the sole member of the rubivirus genus. Rubella virus has a small genome composed of single‐stranded RNA and produces only five proteins. The rubella virus replication cycle takes place entirely within the cytoplasm of the infected cell. Rubella virus establishes a body‐wide or systemic infection that is manifested by mild symptoms including rash, lymph node swelling and low‐grade fever. However, rubella virus is an important human pathogen because it causes a spectrum of serious birth defects known collectively as congenital rubella syndrome (CRS) when a mother lacking immunity is infected during the first trimester of pregnancy. CRS can include blindness, deafness, mental retardation, heart malformations and endocrine dysfunctions. Before development of effective live, attenuated vaccines, rubella virus was the leading teratogenic agent of an infectious nature. Through use of these vaccines, rubella and CRS are controlled in much, but not all, of the world and are targeted for elimination in the Western Hemisphere and Europe. Key Concepts: Rubella virus causes a benign systemic illness characterised by a rash, but is a dangerous teratogen when infection occurs during pregnancy. Fetal infection by rubella virus results in congenital rubella syndrome, a constellation of serious birth defects, particularly deafness, blindness and mental retardation. Rubella virus is classified in the Togaviridae family and is the only member of the rubivirus genus. Rubella virions are pleiomorphic, approximately 70 nm in diameter and consist of a quasispherical capsid containing the genome RNA surrounded by an envelope composed of a lipid bilayer from which protrude glycoprotein spikes. The rubella virus genome is a plus‐polarity RNA, 10 000 nucleotides in length, which encodes only five proteins: P150 and P90, both of which participate in RNA replication in the infected cells, and capsid (C) and envelope glycoproteins 1 and 2 (E1 and E2) which comprise the virion. In the infected cell, rubella virus replication takes place entirely within the cytoplasm. In the infected cell, rubella virus RNA replication, which proceeds through an RNA intermediate, takes place in association with cell membranes. In the infected cell, rubella virion formation takes place in association with the Golgi apparatus and virions are released by exocytosis. Rubella virus isolates worldwide cluster into 13 genotypes that fit into two distinct clades with an overall diversity at the nucleotide level of approximately 10%, a very low level for an RNA virus. Live, attenuated rubella virus vaccines, available since approximately 1970, have been used successfully to control or eliminate rubella in developed countries whereas implementation of these vaccines is progressing, but not complete, in undeveloped countries of the world.

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Three-dimensional structure of Rubella virus factories

Cited by 55 publications

References 72 publications

Involvement of p32 and Microtubules in Alteration of Mitochondrial Functions by Rubella Virus

Involvement of p32 and Microtubules in Alteration of Mitochondrial Functions by Rubella Virus

Three-Dimensional Imaging of Viral Infections

Rubella Virus

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