A giant virus infecting the amoeboflagellate Naegleria

Arthofer, Patrick; Panhölzl, Florian; Delafont, Vincent; Hay, Alban; Reipert, Siegfried; Cyran, Norbert; Wienkoop, Stefanie; Willemsen, Anouk; Sifaoui, Ines; Arberas-Jiménez, Iñigo; Schulz, Frederik; Lorenzo-Morales, Jacob; Horn, Matthias

doi:10.1038/s41467-024-47308-2

A giant virus infecting the amoeboflagellate Naegleria

Journal Article · Wed Apr 24 00:00:00 EDT 2024 · Nature Communications

DOI:https://doi.org/10.1038/s41467-024-47308-2· OSTI ID:2407306

^[1]; Panhölzl, Florian ^[1]; ^[2]; ^[2]; Reipert, Siegfried ^[1]; Cyran, Norbert ^[1]; Wienkoop, Stefanie ^[1]; ^[1]; Sifaoui, Ines ^[3]; Arberas-Jiménez, Iñigo ^[4]; ^[5]; Lorenzo-Morales, Jacob ^[3]; ^[1]

Univ. of Vienna (Austria)
University of Poitiers (France); Centre National de la Recherche Scientifique-Mixed Organizations (CNRS-UMR) (France)
University of La Laguna (Spain); Univ. Carlos III de Madrid (Spain)
University of La Laguna (Spain)
USDOE Joint Genome Institute (JGI), Berkeley, CA (United States)

Giant viruses (Nucleocytoviricota) are significant lethality agents of various eukaryotic hosts. Although metagenomics indicates their ubiquitous distribution, available giant virus isolates are restricted to a very small number of protist and algal hosts. Here we report on the first viral isolate that replicates in the amoeboflagellate Naegleria. This genus comprises the notorious human pathogen Naegleria fowleri, the causative agent of the rare but fatal primary amoebic meningoencephalitis. We have elucidated the structure and infection cycle of this giant virus, Catovirus naegleriensis (a.k.a. Naegleriavirus, NiV), and show its unique adaptations to its Naegleria host using fluorescence in situ hybridization, electron microscopy, genomics, and proteomics. Naegleriavirus is only the fourth isolate of the highly diverse subfamily Klosneuvirinae, and like its relatives the NiV genome contains a large number of translation genes, but lacks transfer RNAs (tRNAs). NiV has acquired genes from its Naegleria host, which code for heat shock proteins and apoptosis inhibiting factors, presumably for host interactions. Notably, NiV infection was lethal to all Naegleria species tested, including the human pathogen N. fowleri. This study expands our experimental framework for investigating giant viruses and may help to better understand the basic biology of the human pathogen N. fowleri.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2407306

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 15; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (75)

tRNAscan-SE: Searching for tRNA Genes in Genomic Sequences Chan, Patricia P.; Lowe, Todd M. Methods in Molecular Biology https://doi.org/10.1007/978-1-4939-9173-0_1	book	January 2019
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Bradford, Marion M. Analytical Biochemistry, Vol. 72, Issue 1-2 https://doi.org/10.1016/0003-2697(76)90527-3	journal	May 1976
The Domain-specific Probe EUB338 is Insufficient for the Detection of all Bacteria: Development and Evaluation of a more Comprehensive Probe Set Daims, Holger; Brühl, Andreas; Amann, Rudolf Systematic and Applied Microbiology, Vol. 22, Issue 3 https://doi.org/10.1016/S0723-2020(99)80053-8	journal	September 1999
Structural and Proteomic Characterization of the Initiation of Giant Virus Infection Schrad, Jason R.; Abrahão, Jônatas S.; Cortines, Juliana R. Cell, Vol. 181, Issue 5 https://doi.org/10.1016/j.cell.2020.04.032	journal	May 2020
Giant viruses and their mobile genetic elements: the molecular symbiosis hypothesis Filée, Jonathan Current Opinion in Virology, Vol. 33 https://doi.org/10.1016/j.coviro.2018.07.013	journal	December 2018
Alohomora! What the entry mechanisms tell us about the evolution and diversification of giant viruses and their hosts de Souza, Gabriel Augusto Pires; Queiroz, Victória Fulgêncio; Coelho, Luiz Felipe Leomil Current Opinion in Virology, Vol. 47 https://doi.org/10.1016/j.coviro.2021.02.003	journal	April 2021
BlastKOALA and GhostKOALA: KEGG Tools for Functional Characterization of Genome and Metagenome Sequences Kanehisa, Minoru; Sato, Yoko; Morishima, Kanae Journal of Molecular Biology, Vol. 428, Issue 4 https://doi.org/10.1016/j.jmb.2015.11.006	journal	February 2016
A Completely Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at its Core Zimmermann, Lukas; Stephens, Andrew; Nam, Seung-Zin Journal of Molecular Biology, Vol. 430, Issue 15 https://doi.org/10.1016/j.jmb.2017.12.007	journal	July 2018
Is Naegleria fowleri an Emerging Parasite? Maciver, Sutherland K.; Piñero, Jose E.; Lorenzo-Morales, Jacob Trends in Parasitology, Vol. 36, Issue 1 https://doi.org/10.1016/j.pt.2019.10.008	journal	January 2020
Combatting African Animal Trypanosomiasis (AAT) in livestock: The potential role of trypanotolerance Yaro, M.; Munyard, K. A.; Stear, M. J. Veterinary Parasitology, Vol. 225 https://doi.org/10.1016/j.vetpar.2016.05.003	journal	July 2016
Atomic force microscopy investigation of the giant mimivirus Kuznetsov, Yuri G.; Xiao, Chuan; Sun, Siyang Virology, Vol. 404, Issue 1 https://doi.org/10.1016/j.virol.2010.05.007	journal	August 2010
The virion of Cafeteria roenbergensis virus (CroV) contains a complex suite of proteins for transcription and DNA repair Fischer, Matthias G.; Kelly, Isabelle; Foster, Leonard J. Virology, Vol. 466-467 https://doi.org/10.1016/j.virol.2014.05.029	journal	October 2014
Infection cycles of large DNA viruses: Emerging themes and underlying questions Mutsafi, Yael; Fridmann-Sirkis, Yael; Milrot, Elad Virology, Vol. 466-467 https://doi.org/10.1016/j.virol.2014.05.037	journal	October 2014
Marine viruses and their biogeochemical and ecological effects Fuhrman, Jed A. Nature, Vol. 399, Issue 6736 https://doi.org/10.1038/21119	journal	June 1999
The virophage as a unique parasite of the giant mimivirus La Scola, Bernard; Desnues, Christelle; Pagnier, Isabelle Nature, Vol. 455, Issue 7209 https://doi.org/10.1038/nature07218	journal	August 2008
MIMIVIRE is a defence system in mimivirus that confers resistance to virophage Levasseur, Anthony; Bekliz, Meriem; Chabrière, Eric Nature, Vol. 531, Issue 7593 https://doi.org/10.1038/nature17146	journal	February 2016
Marine viruses — major players in the global ecosystem Suttle, Curtis A. Nature Reviews Microbiology, Vol. 5, Issue 10 https://doi.org/10.1038/nrmicro1750	journal	October 2007
Tailed giant Tupanvirus possesses the most complete translational apparatus of the known virosphere Abrahão, Jônatas; Silva, Lorena; Silva, Ludmila Santos Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-03168-1	journal	February 2018
Dynamic genome evolution and complex virocell metabolism of globally-distributed giant viruses Moniruzzaman, Mohammad; Martinez-Gutierrez, Carolina A.; Weinheimer, Alaina R. Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-15507-2	journal	April 2020
Near-atomic, non-icosahedrally averaged structure of giant virus Paramecium bursaria chlorella virus 1 Shao, Qianqian; Agarkova, Irina V.; Noel, Eric A. Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-34218-4	journal	October 2022
Systematic evaluation of horizontal gene transfer between eukaryotes and viruses Irwin, Nicholas A. T.; Pittis, Alexandros A.; Richards, Thomas A. Nature Microbiology, Vol. 7, Issue 2 https://doi.org/10.1038/s41564-021-01026-3	journal	December 2021
Giant virus diversity and host interactions through global metagenomics Schulz, Frederik; Roux, Simon; Paez-Espino, David Nature, Vol. 578, Issue 7795 https://doi.org/10.1038/s41586-020-1957-x	journal	January 2020
Widespread endogenization of giant viruses shapes genomes of green algae Moniruzzaman, Mohammad; Weinheimer, Alaina R.; Martinez-Gutierrez, Carolina A. Nature, Vol. 588, Issue 7836 https://doi.org/10.1038/s41586-020-2924-2	journal	November 2020
Four novel algal virus genomes discovered from Yellowstone Lake metagenomes Zhang, Weijia; Zhou, Jinglie; Liu, Taigang Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep15131	journal	October 2015
Vaccinia-like cytoplasmic replication of the giant Mimivirus Mutsafi, Y.; Zauberman, N.; Sabanay, I. Proceedings of the National Academy of Sciences, Vol. 107, Issue 13 https://doi.org/10.1073/pnas.0912737107	journal	March 2010
Giant virus with a remarkable complement of genes infects marine zooplankton Fischer, M. G.; Allen, M. J.; Wilson, W. H. Proceedings of the National Academy of Sciences, Vol. 107, Issue 45 https://doi.org/10.1073/pnas.1007615107	journal	October 2010
Virophage control of antarctic algal host-virus dynamics Yau, S.; Lauro, F. M.; DeMaere, M. Z. Proceedings of the National Academy of Sciences, Vol. 108, Issue 15 https://doi.org/10.1073/pnas.1018221108	journal	March 2011
In-depth study of Mollivirus sibericum , a new 30,000-y-old giant virus infecting Acanthamoeba Legendre, Matthieu; Lartigue, Audrey; Bertaux, Lionel Proceedings of the National Academy of Sciences, Vol. 112, Issue 38 https://doi.org/10.1073/pnas.1510795112	journal	September 2015
Diversification of giant and large eukaryotic dsDNA viruses predated the origin of modern eukaryotes Guglielmini, Julien; Woo, Anthony C.; Krupovic, Mart Proceedings of the National Academy of Sciences, Vol. 116, Issue 39 https://doi.org/10.1073/pnas.1912006116	journal	September 2019
Defensive symbiosis against giant viruses in amoebae Arthofer, Patrick; Delafont, Vincent; Willemsen, Anouk Proceedings of the National Academy of Sciences, Vol. 119, Issue 36 https://doi.org/10.1073/pnas.2205856119	journal	August 2022
Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences Li, W.; Godzik, A. Bioinformatics, Vol. 22, Issue 13 https://doi.org/10.1093/bioinformatics/btl158	journal	May 2006
trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses Capella-Gutierrez, S.; Silla-Martinez, J. M.; Gabaldon, T. Bioinformatics, Vol. 25, Issue 15 https://doi.org/10.1093/bioinformatics/btp348	journal	June 2009
Unipro UGENE: a unified bioinformatics toolkit Okonechnikov, Konstantin; Golosova, Olga; Fursov, Mikhail Bioinformatics, Vol. 28, Issue 8 https://doi.org/10.1093/bioinformatics/bts091	journal	February 2012
Adding unaligned sequences into an existing alignment using MAFFT and LAST Katoh, Kazutaka; Frith, Martin C. Bioinformatics, Vol. 28, Issue 23 https://doi.org/10.1093/bioinformatics/bts578	journal	September 2012
Infernal 1.1: 100-fold faster RNA homology searches Nawrocki, E. P.; Eddy, S. R. Bioinformatics, Vol. 29, Issue 22 https://doi.org/10.1093/bioinformatics/btt509	journal	September 2013
Prokka: rapid prokaryotic genome annotation Seemann, T. Bioinformatics, Vol. 30, Issue 14 https://doi.org/10.1093/bioinformatics/btu153	journal	March 2014
New versatile staining reagents for biological transmission electron microscopy that substitute for uranyl acetate Nakakoshi, M.; Nishioka, H.; Katayama, E. Journal of Electron Microscopy, Vol. 60, Issue 6 https://doi.org/10.1093/jmicro/dfr084	journal	December 2011
A Novel Group of Dynamin-Related Proteins Shared by Eukaryotes and Giant Viruses Is Able to Remodel Mitochondria From Within the Matrix Sheikh, Shaghayegh; Pánek, Tomáš; Gahura, Ondřej Molecular Biology and Evolution, Vol. 40, Issue 6 https://doi.org/10.1093/molbev/msad134	journal	June 2023
FastTree: Computing Large Minimum Evolution Trees with Profiles instead of a Distance Matrix Price, M. N.; Dehal, P. S.; Arkin, A. P. Molecular Biology and Evolution, Vol. 26, Issue 7 https://doi.org/10.1093/molbev/msp077	journal	April 2009
SeaView Version 4: A Multiplatform Graphical User Interface for Sequence Alignment and Phylogenetic Tree Building Gouy, M.; Guindon, S.; Gascuel, O. Molecular Biology and Evolution, Vol. 27, Issue 2 https://doi.org/10.1093/molbev/msp259	journal	October 2009
IQ-TREE: A Fast and Effective Stochastic Algorithm for Estimating Maximum-Likelihood Phylogenies Nguyen, Lam-Tung; Schmidt, Heiko A.; von Haeseler, Arndt Molecular Biology and Evolution, Vol. 32, Issue 1 https://doi.org/10.1093/molbev/msu300	journal	November 2014
The InterPro protein families and domains database: 20 years on Blum, Matthias; Chang, Hsin-Yu; Chuguransky, Sara Nucleic Acids Research, Vol. 49, Issue D1 https://doi.org/10.1093/nar/gkaa977	journal	November 2020
Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation Letunic, Ivica; Bork, Peer Nucleic Acids Research, Vol. 49, Issue W1 https://doi.org/10.1093/nar/gkab301	journal	April 2021
MUSCLE: multiple sequence alignment with high accuracy and high throughput Edgar, R. C. Nucleic Acids Research, Vol. 32, Issue 5, p. 1792-1797 https://doi.org/10.1093/nar/gkh340	journal	March 2004
eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses Huerta-Cepas, Jaime; Szklarczyk, Damian; Heller, Davide Nucleic Acids Research, Vol. 47, Issue D1 https://doi.org/10.1093/nar/gky1085	journal	November 2018
Terrace Aware Data Structure for Phylogenomic Inference from Supermatrices Chernomor, Olga; von Haeseler, Arndt; Minh, Bui Quang Systematic Biology, Vol. 65, Issue 6 https://doi.org/10.1093/sysbio/syw037	journal	April 2016
Modeling Site Heterogeneity with Posterior Mean Site Frequency Profiles Accelerates Accurate Phylogenomic Estimation Wang, Huai-Chun; Minh, Bui Quang; Susko, Edward Systematic Biology, Vol. 67, Issue 2 https://doi.org/10.1093/sysbio/syx068	journal	August 2017
Phagocytosis and Pinocytosis in Acanthamoeba castellanii Chambers, J. A.; Thompson, J. E. Journal of General Microbiology, Vol. 92, Issue 2 https://doi.org/10.1099/00221287-92-2-246	journal	February 1976
Circos: An information aesthetic for comparative genomics Krzywinski, M.; Schein, J.; Birol, I. Genome Research, Vol. 19, Issue 9 https://doi.org/10.1101/gr.092759.109	journal	June 2009
Canu: scalable and accurate long-read assembly via adaptive k -mer weighting and repeat separation Koren, Sergey; Walenz, Brian P.; Berlin, Konstantin Genome Research, Vol. 27, Issue 5 https://doi.org/10.1101/gr.215087.116	journal	March 2017
Improved axenization method reveals complexity of symbiotic associations between bacteria and acanthamoebae: An improved method for the axenization of amoebae Lagkouvardos, Ilias; Shen, Jie; Horn, Matthias Environmental Microbiology Reports, Vol. 6, Issue 4 https://doi.org/10.1111/1758-2229.12162	journal	April 2014
Megaviruses contain various genes encoding for eukaryotic vesicle trafficking factors Khalifeh, Dany; Neveu, Emilie; Fasshauer, Dirk Traffic, Vol. 23, Issue 8 https://doi.org/10.1111/tra.12860	journal	June 2022
A Giant Virus in Amoebae Scola, B. L. Science, Vol. 299, Issue 5615 https://doi.org/10.1126/science.1081867	journal	March 2003
A Virophage at the Origin of Large DNA Transposons Fischer, M. G.; Suttle, C. A. Science, Vol. 332, Issue 6026 https://doi.org/10.1126/science.1199412	journal	March 2011
Pandoraviruses: Amoeba Viruses with Genomes Up to 2.5 Mb Reaching That of Parasitic Eukaryotes Philippe, N.; Legendre, M.; Doutre, G. Science, Vol. 341, Issue 6143 https://doi.org/10.1126/science.1239181	journal	July 2013
Giant viruses with an expanded complement of translation system components Schulz, Frederik; Yutin, Natalya; Ivanova, Natalia N. Science, Vol. 356, Issue 6333 https://doi.org/10.1126/science.aal4657	journal	April 2017
Naegleria fowleri: Pathogenesis, Diagnosis, and Treatment Options Grace, Eddie; Asbill, Scott; Virga, Kris Antimicrobial Agents and Chemotherapy, Vol. 59, Issue 11 https://doi.org/10.1128/AAC.01293-15	journal	August 2015
The Genome of the Amoeba Symbiont "Candidatus Amoebophilus asiaticus" Reveals Common Mechanisms for Host Cell Interaction among Amoeba-Associated Bacteria Schmitz-Esser, S.; Tischler, P.; Arnold, R. Journal of Bacteriology, Vol. 192, Issue 4 https://doi.org/10.1128/JB.01379-09	journal	December 2009
Efficiency in Complexity: Composition and Dynamic Nature of Mimivirus Replication Factories Fridmann-Sirkis, Yael; Milrot, Elad; Mutsafi, Yael Journal of Virology, Vol. 90, Issue 21 https://doi.org/10.1128/JVI.01319-16	journal	November 2016
Isolation of Yasminevirus, the First Member of Klosneuvirinae Isolated in Coculture with Vermamoeba vermiformis , Demonstrates an Extended Arsenal of Translational Apparatus Components Bajrai, Leena Hussein; Mougari, Saïd; Andreani, Julien Journal of Virology, Vol. 94, Issue 1 https://doi.org/10.1128/JVI.01534-19	journal	October 2019
Mimivirus Fibrils Are Important for Viral Attachment to the Microbial World by a Diverse Glycoside Interaction Repertoire Rodrigues, Rodrigo Araújo Lima; dos Santos Silva, Ludmila Karen; Dornas, Fábio Pio Journal of Virology, Vol. 89, Issue 23 https://doi.org/10.1128/JVI.01976-15	journal	September 2015
Fluorescent-oligonucleotide probing of whole cells for determinative, phylogenetic, and environmental studies in microbiology. Amann, R. I.; Krumholz, L.; Stahl, D. A. Journal of Bacteriology, Vol. 172, Issue 2 https://doi.org/10.1128/jb.172.2.762-770.1990	journal	February 1990
Giant viruses, giant chimeras: The multiple evolutionary histories of Mimivirus genes Moreira, David; Brochier-Armanet, Céline BMC Evolutionary Biology, Vol. 8, Issue 1 https://doi.org/10.1186/1471-2148-8-12	journal	January 2008
Multiple evolutionary origins of giant viruses Koonin, Eugene V.; Yutin, Natalya F1000Research, Vol. 7 https://doi.org/10.12688/f1000research.16248.1	journal	January 2018
Agitation Modules: Flexible Means to Accelerate Automated Freeze Substitution Reipert, Siegfried; Goldammer, Helmuth; Richardson, Christine Journal of Histochemistry & Cytochemistry, Vol. 66, Issue 12 https://doi.org/10.1369/0022155418786698	journal	July 2018
Structural Studies of the Giant Mimivirus Xiao, Chuan; Kuznetsov, Yurii G.; Sun, Siyang PLoS Biology, Vol. 7, Issue 4 https://doi.org/10.1371/journal.pbio.1000092	journal	April 2009
Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads Wick, Ryan R.; Judd, Louise M.; Gorrie, Claire L. PLOS Computational Biology, Vol. 13, Issue 6 https://doi.org/10.1371/journal.pcbi.1005595	journal	June 2017
Ultrastructural Characterization of the Giant Volcano-like Virus Factory of Acanthamoeba polyphaga Mimivirus Suzan-Monti, Marie; Scola, Bernard La; Barrassi, Lina PLoS ONE, Vol. 2, Issue 3 https://doi.org/10.1371/journal.pone.0000328	journal	March 2007
The Giant Cafeteria roenbergensis Virus That Infects a Widespread Marine Phagocytic Protist Is a New Member of the Fourth Domain of Life Colson, Philippe; Gimenez, Gregory; Boyer, Mickaël PLoS ONE, Vol. 6, Issue 4 https://doi.org/10.1371/journal.pone.0018935	journal	April 2011
Morphological and Genomic Features of the New Klosneuvirinae Isolate Fadolivirus IHUMI-VV54 Andreani, Julien; Schulz, Frederik; Di Pinto, Fabrizio Frontiers in Microbiology, Vol. 12 https://doi.org/10.3389/fmicb.2021.719703	journal	September 2021
Subcellular Phenotyping: Using Proteomics to Quantitatively Link Subcellular Leaf Protein and Organelle Distribution Analyses of Pisum sativum Cultivars Schneider, Sebastian; Harant, Dominik; Bachmann, Gert Frontiers in Plant Science, Vol. 10 https://doi.org/10.3389/fpls.2019.00638	journal	May 2019
Host Range and Coding Potential of Eukaryotic Giant Viruses Sun, Tsu-Wang; Yang, Chia-Ling; Kao, Tzu-Tong Viruses, Vol. 12, Issue 11 https://doi.org/10.3390/v12111337	journal	November 2020
A novel group of dynamin-related proteins shared by eukaryotes and giant viruses is able to remodel mitochondria from within the matrix Panek, Tomas figshare https://doi.org/10.6084/m9.figshare.22769669.v1	dataset	January 2023
Phylogenetic tree files of Naegleriavirus proteins most similar to protist proteins Arthofer, Patrick figshare https://doi.org/10.6084/m9.figshare.25117901.v1	dataset	January 2024
The kinetoplastid-infecting Bodo saltans virus (BsV), a window into the most abundant giant viruses in the sea Deeg, Christoph M.; Chow, Cheryl-Emiliane T.; Suttle, Curtis A. eLife, Vol. 7 https://doi.org/10.7554/eLife.33014	journal	March 2018