Structural and Proteomic Characterization of the Initiation of Giant Virus Infection

Schrad, Jason R.; Abrahão, Jônatas Santos; Cortines, Juliana R.; Parent, Kristin N.

doi:10.1016/j.cell.2020.04.032

Cited by 44 publications

(59 citation statements)

References 93 publications

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“…For viruses that replicate in the nucleus, the viral genome needs to enter the nucleus via a nuclear pore (Smith and Helenius, 2004). Multiple distinct strategies are utilized, largely depending on the viral genome size (Schrad et al, 2020). Viral capsids of viruses with smaller genomes enter the nucleus, while for viruses with large genomes, the docking of nucleocapsids to a nuclear pore complex causes a partial disruption of the capsid or induces a minimal change in the viral capsid, allowing the transit of the DNA genome into the nucleus (Lakadamyali et al, 2003;Xie et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

The compound packaged in virions is the key to trigger host glycolysis machinery for virus life cycle in the cytoplasm

2021

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Summary Viruses depend on the host metabolic machinery to complete their life cycle in the host cytoplasm. However, the key viral factors initiating the host machinery after the virus enters the cytoplasm remain unclear. Here, we found that compounds packaged in the virions of white spot syndrome virus, such as palmitic amide, could trigger the viral life cycle in the host cytoplasm. Palmitic amide promoted virus infection by enhancing host glycolysis by binding to triosephosphate isomerase to enhance its enzymatic activity. The glycolysis enhancement resulted in lactate accumulation, thereby promoting hypoxia-inducible factor 1 (HIF-1) expression. HIF-1 upregulation further enhanced glycolysis, which in turn promoted virus infection. Therefore, our study presented novel insight into the initiation of the virus life cycle in host cells.

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Section: Discussionmentioning

confidence: 99%

The compound packaged in virions is the key to trigger host glycolysis machinery for virus life cycle in the cytoplasm

2021

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“…After the cell's invasion, the next step in the replication cycle of viruses is the exposure of their genome to transcription and translation machinery capable of acting on it. During the infection cycle of GV in amoebas, 8 hours after viral adsorption pseudo-organelles called viral factories are observed (Abrahão et al, 2018;Schrad et al, 2020). This region concentrates all the factors necessary for the replication and packaging of the genome during the assembly of viral particles.…”

Section: Discussionmentioning

confidence: 99%

Paving the way towards understanding the inflammatory pathways triggered by giant viruses in mammalian cells: effect of mimivirus-cell interactions on IκBα degradation

Oliveira

Essus

et al. 2021

Preprint

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Even after two decades since the identification of the first giant virus, the Acanthamoeba polyphaga mimivirus (APMV), it still elude scientists. Their gigantic size and genome are unique in the whole virosphere, and many aspects of their biology are still unknown, including their possible hosts. They are cultivated in laboratories using Acanthamoeba cells as hosts, but little is known about the infectivity of these giant viruses in vertebrate cells. However, there is evidence of the possible involvement of APMV in pneumonia and activation of inflammatory pathways. Among the hundreds of prospected giant viruses members is Tupanvirus, isolated in Brazil. Its particles have a characteristically large size varying between 1.2 to 2 μm and are covered by fibrils. In the present work, we aim to study the consequences of the incubation of APMV and Tupanvirus with mammalian cells. These cells express Toll-like receptors (TLR) that are capable of recognizing lipopolysaccharides, favoring the internalization of the antigen and activation of the inflammatory system. We used a lineage of human lung adenocarcinoma cells (A549) to evaluate possible effects of TLR activation by the giant viruses and if we could detect the probable cause of the said giant-virus dependent pneumonia. Our results show that APMV and Tupanvirus (TPV) activate cellular receptors related to the Toll-like 4 type-induced inflammatory response and that the A549 cells are capable of internalizing the latter virus. Therefore, this study brings new insights into the possible interactions established between mimiviruses (here represented by APMV and Tupanvirus) and members of the innate cellular immune response.

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“…Due to the size of the virions, structural analyses have provided some insights into their icosahedral capsid structure 2,[13][14][15] but little is known about the packaging of the 1.2 Mb dsDNA genome 16 . Inside the capsids, a lipidic membrane delineates an internal compartment (~350 nm in diameter), we refer to as the nucleoid, containing the viral genome, together with all the proteins necessary to initiate the replicative cycle within the host cytoplasm [17][18][19] .…”

Section: Mainmentioning

confidence: 99%

“…Acanthamoeba cells engulf Mimivirus particles, fooled by their bacteria-like size and the sweet taste of the heavily glycosylated decorating fibrils 1,6 . Once in the vacuole, the Stargate portal located at one specific vertex of the icosahedron opens up 20 , enabling the viral membrane to fuse with that of the phagosome to deliver the nucleoid into the host cytoplasm 17,19 . Subsequently, the nucleoid starts losing its electron dense appearance, transcription begins and the early viral factory is formed 18,21,22 .…”

Section: Mainmentioning

confidence: 99%

The Mimivirus 1.2 Mb dsDNA genome is elegantly organized into a nuclear-like weapon

Abergel¹,

Casares²,

Quemin³

et al. 2021

Preprint

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Mimivirus is the prototype of the Mimiviridae family of giant dsDNA viruses, initially isolated in Acanthamoeba1. Little is known about the organization of the viral genome inside the membrane limited nucleoid2 and whether unpacking or other rearrangements are required prior to transcription and replication. Here we show that opening of its large icosahedral capsid in vitro leads to the release of electron dense, 30 nm diameter rod-shaped objects that appear to be expelled from the particles and unwinding. We developed a purification procedure and characterized the detailed structure at various stages of decompaction using cryo-electron microscopy single particle analyses and its composition by proteomics. This revealed that the viral genome is encased into a helical protein shell surprisingly made of the two GMC-type oxydoreductases that are also the major components of the glycosylated fibrils surrounding the capsid3. The 1.2 Mb genome is folded to follow a 5- or 6-start left-handed helix, depending on the nature of the GMC-oxydoreductase, with each helical strand lining the interior of the protein shell. Proteomic analyses of the purified genomic fibre revealed the presence of several RNA polymerase subunits as well as additional proteins involved in genome compaction that can fit into the central channel of the protein shield. Such an elegant supramolecular organization represents a remarkable evolutionary solution for packaging while protecting the viral genome, in a state ready for immediate transcription upon unwinding in the host cytoplasm. We expect that a dedicated energy-driven machinery is required for the assembly of this rod-shaped giant viral chromosome and its further compaction in the membrane limited electron dense nucleoid, characteristic of the mature Mimivirus particles2,4,5.The parsimonious implication of the same protein in two functionally unrelated substructures of the virion is also unexpected for a giant virus with a thousand genes at its disposal.

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Structural and Proteomic Characterization of the Initiation of Giant Virus Infection

Cited by 44 publications

References 93 publications

The compound packaged in virions is the key to trigger host glycolysis machinery for virus life cycle in the cytoplasm

The compound packaged in virions is the key to trigger host glycolysis machinery for virus life cycle in the cytoplasm

Paving the way towards understanding the inflammatory pathways triggered by giant viruses in mammalian cells: effect of mimivirus-cell interactions on IκBα degradation

The Mimivirus 1.2 Mb dsDNA genome is elegantly organized into a nuclear-like weapon

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