The giant mimivirus 1.2 Mb genome is elegantly organized into a 30 nm diameter helical protein shield
- Aix-Marseille University, CNRS-AMU UMR7256, France
- Univ. Grenoble Alpes, CNRS, CEA,, France
- University of Hamburg, Germany
- Université Grenoble Alpes, France
Abstract
Mimivirus is the prototype of the Mimiviridae family of giant dsDNA viruses. Little is known about the organization of the 1.2 Mb genome inside the membrane-limited nucleoid filling the ~0.5 µm icosahedral capsids. Cryo-electron microscopy, cryo-electron tomography and proteomics revealed that it is encased into a ~30 nm diameter helical protein shell surprisingly composed of two GMC-type oxidoreductases, which also form the glycosylated fibrils decorating the capsid. The genome is arranged in 5- or 6-start left-handed super-helices, with each DNA-strand lining the central channel. This luminal channel of the nucleoprotein fiber is wide enough to accommodate oxidative stress proteins and RNA polymerase subunits identified by proteomics. Such elegant supramolecular organization would represent a remarkable evolutionary strategy for packaging and protecting the genome, in a state ready for immediate transcription upon unwinding in the host cytoplasm. The parsimonious use of the same protein in two unrelated substructures of the virion is unexpected for a giant virus with thousand genes at its disposal.
Data availability
Mimivirus reunion genome has been deposited under the following accession number: BankIt2382307 Seq1 MW004169.3D reconstruction maps and the corresponding PDB have been deposited to EMDB (Deposition number Cl1a: 7YX4, EMD-14354; Cl1a focused refined: D_1292117739; Cl3a: 7YX5, EMD-14355; Cl2: 7YX3, EMD-14353).The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD021585 and 10.6019/PXD021585.The tomograms have been deposited in EMPIAR under accession number 1131 and tomograms video are provided with the article.
Article and author information
Author details
Funding
European Research Council (832601)
- Chantal Abergel
Agence Nationale de la Recherche (ANR-16-CE11-0033-01)
- Chantal Abergel
Agence Nationale de la Recherche (ANR-10-INBS-08-01)
- Yohann Couté
Agence Nationale de la Recherche (ANR-17-EURE-0003)
- Yohann Couté
Wellcome Trust (107806/Z/15/Z)
- Kay Grünewald
Deutsche Forschungsgemeinschaft (INST 152/772-1|152/774-1|152/775-1|152/776-1)
- Kay Grünewald
Alexander von Humboldt-Stiftung (FRA 1200789 HFST-P)
- Emmanuelle RJ Quemin
Agence Nationale de la Recherche (ANR-10-INBS-04)
- Chantal Abergel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Villalta et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,491
- views
-
- 970
- downloads
-
- 19
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
The giant mimivirus 1.2 Mb genome is elegantly organized into a 30 nm diameter helical protein shield
eLife 11:e77607.
https://doi.org/10.7554/eLife.77607
Further reading
-
- Microbiology and Infectious Disease
The persistence of latent viral reservoirs remains the major obstacle to eradicating human immunodeficiency virus (HIV). We herein found that ICP34.5 can act as an antagonistic factor for the reactivation of HIV latency by herpes simplex virus type I (HSV-1), and thus recombinant HSV-1 with ICP34.5 deletion could more effectively reactivate HIV latency than its wild-type counterpart. Mechanistically, HSV-ΔICP34.5 promoted the phosphorylation of HSF1 by decreasing the recruitment of protein phosphatase 1 (PP1α), thus effectively binding to the HIV LTR to reactivate the latent reservoirs. In addition, HSV-ΔICP34.5 enhanced the phosphorylation of IKKα/β through the degradation of IκBα, leading to p65 accumulation in the nucleus to elicit NF-κB pathway-dependent reactivation of HIV latency. Then, we constructed the recombinant HSV-ΔICP34.5 expressing simian immunodeficiency virus (SIV) env, gag, or the fusion antigen sPD1-SIVgag as a therapeutic vaccine, aiming to achieve a functional cure by simultaneously reactivating viral latency and eliciting antigen-specific immune responses. Results showed that these constructs effectively elicited SIV-specific immune responses, reactivated SIV latency, and delayed viral rebound after the interruption of antiretroviral therapy (ART) in chronically SIV-infected rhesus macaques. Collectively, these findings provide insights into the rational design of HSV-vectored therapeutic strategies for pursuing an HIV functional cure.
-
- Biochemistry and Chemical Biology
- Microbiology and Infectious Disease
Teichoic acids (TA) are linear phospho-saccharidic polymers and important constituents of the cell envelope of Gram-positive bacteria, either bound to the peptidoglycan as wall teichoic acids (WTA) or to the membrane as lipoteichoic acids (LTA). The composition of TA varies greatly but the presence of both WTA and LTA is highly conserved, hinting at an underlying fundamental function that is distinct from their specific roles in diverse organisms. We report the observation of a periplasmic space in Streptococcus pneumoniae by cryo-electron microscopy of vitreous sections. The thickness and appearance of this region change upon deletion of genes involved in the attachment of TA, supporting their role in the maintenance of a periplasmic space in Gram-positive bacteria as a possible universal function. Consequences of these mutations were further examined by super-resolved microscopy, following metabolic labeling and fluorophore coupling by click chemistry. This novel labeling method also enabled in-gel analysis of cell fractions. With this approach, we were able to titrate the actual amount of TA per cell and to determine the ratio of WTA to LTA. In addition, we followed the change of TA length during growth phases, and discovered that a mutant devoid of LTA accumulates the membrane-bound polymerized TA precursor.
