A phylogenomic framework for charting the diversity and evolution of giant viruses

Large DNA viruses of the phylum Nucleocytoviricota have recently emerged as important members of ecosystems around the globe that challenge traditional views of viral complexity. Numerous members of this phylum that cannot be classified within established families have recently been reported, and there is presently a strong need for a robust phylogenomic and taxonomic framework for these viruses. Here, we report a comprehensive phylogenomic analysis of the Nucleocytoviricota, present a set of giant virus orthologous groups (GVOGs) together with a benchmarked reference phylogeny, and delineate a hierarchical taxonomy within this phylum. We show that the majority of Nucleocytoviricota diversity can be partitioned into 6 orders, 32 families, and 344 genera, substantially expanding the number of currently recognized taxonomic ranks for these viruses. We integrate our results within a taxonomy that has been adopted for all viruses to establish a unifying framework for the study of Nucleocytoviricota diversity, evolution, and environmental distribution.

RNA Sequencing of Medusavirus Suggests Remodeling of the Host Nuclear Environment at an Early Infection Stage

Medusavirus is an amoeba-infecting giant virus that was isolated from a hot spring in Japan. It belongs to the proposed family “ Medusaviridae ” in the phylum Nucleocytoviricota .

Virophage: The hijacker of my hijacker is my friend

The discovery of virophage carries along the proof of existence of a new bio controlling agent in the entire biosystem. The virophage is a parasite to a giant virus and works by hijacking “the giant virus” viral factory, an essential machinery for the giant virus’s replication, leading to a sharp incline of the virophage viral load inside the host cell. Success of the host cell survival against the invading giant virus is shown by the decline of the destroyed cell during lytic stage after virophage co-infection to the giant virus. Virophage has a similar role to the bacteriophage but instead of targeting a bacterium, it targets specifically on virus. Hitherto, the existence of human-borne virophage and interactions of virophage to human microbiome remain elusive, thus future studies are required. This short review will highlight the discovery, types and recent known method of virophage replication. We also added some biological perspectives of the connections and interactions between the virophage and its host to exploit the virophage main role as a biocontrolling agent to pathogenic viruses that are potentially benevolent for human life.

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

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.

Giant Viruses and the Tree of Life

When the first giant virus, the mimivirus, was discovered in 1992, it was misidentified as a bacterium because it was too large to have been a virus by the current understanding. Ever since, biologists have been debating how viruses should be categorized and described. Are they living? Are they something else? What is their place on the tree of life?

Giant Virus-Eukaryote Interactions as Ecological and Evolutionary Driving Forces

Giant DNA viruses of eukaryotes are notable for their extraordinary genome size and coding capacity. Once thought to be oddities in the virus world, these elusive microbes have turned out to be widely occurring in marine, freshwater, and terrestrial ecosystems and are commonly associated with diverse hosts, in particular microbial eukaryotes.

Clandestinovirus: A Giant Virus With Chromatin Proteins and a Potential to Manipulate the Cell Cycle of Its Host Vermamoeba vermiformis

For several decades, the vast world of DNA viruses has been expanding constantly. Various discoveries in this field have broadened our knowledge and revealed that DNA viruses encode many functional features, which were once thought to be exclusive to cellular life. Here, we report the isolation of a giant virus named “clandestinovirus,” grown on the amoebal host Vermamoeba vermiformis. This virus was discovered in a mixed co-culture associated with another giant virus, Faustovirus ST1. Clandestinovirus possesses a linear dsDNA genome of 581,987 base pairs containing 617 genes. Phylogenetically, clandestinovirus is most closely related to Acanthamoeba castellanii medusavirus and was considered a member of the proposed Medusaviridae family. However, clandestinovirus genome is 65% larger than that of medusavirus, emphasizing the considerable genome size variation within this virus family. Functional annotation of the clandestinovirus genes suggests that the virus encodes four core histones. Furthermore, clandestinovirus appears to orchestrate the cell cycle and mitochondrial activities of the infected host by virtue of encoding a panel of protein kinases and phosphatases, and a suite of functionally diverse mitochondrial protein homologs, respectively. Collectively, these observations illuminate a strategy employed by clandestinovirus to optimize the intracellular environment for efficient virus propagation.

Diverse Trajectories Drive the Expression of a Giant Virus in the Oomycete Plant Pathogen Phytophthora parasitica

Giant viruses of amoebas, recently classified in the class Megaviricetes, are a group of viruses that can infect major eukaryotic lineages. We previously identified a set of giant virus sequences in the genome of Phytophthora parasitica, an oomycete and a devastating major plant pathogen. How viral insertions shape the structure and evolution of the invaded genomes is unclear, but it is known that the unprecedented functional potential of giant viruses is the result of an intense genetic interplay with their hosts. We previously identified a set of giant virus sequences in the genome of P. parasitica, an oomycete and a devastating major plant pathogen. Here, we show that viral pieces are found in a 550-kb locus and are organized in three main clusters. Viral sequences, namely RNA polymerases I and II and a major capsid protein, were identified, along with orphan sequences, as a hallmark of giant viruses insertions. Mining of public databases and phylogenetic reconstructions suggest an ancient association of oomycetes and giant viruses of amoeba, including faustoviruses, African swine fever virus (ASFV) and pandoraviruses, and that a single viral insertion occurred early in the evolutionary history of oomycetes prior to the Phytophthora–Pythium radiation, estimated at ∼80 million years ago. Functional annotation reveals that the viral insertions are located in a gene sparse region of the Phytophthora genome, characterized by a plethora of transposable elements (TEs), effectors and other genes potentially involved in virulence. Transcription of viral genes was investigated through analysis of RNA-Seq data and qPCR experiments. We show that most viral genes are not expressed, and that a variety of mechanisms, including deletions, TEs insertions and RNA interference may contribute to transcriptional repression. However, a gene coding a truncated copy of RNA polymerase II along a set of neighboring sequences have been shown to be expressed in a wide range of physiological conditions, including responses to stress. These results, which describe for the first time the endogenization of a giant virus in an oomycete, contribute to challenge our view of Phytophthora evolution.

ViralRecall—A Flexible Command-Line Tool for the Detection of Giant Virus Signatures in ‘Omic Data

Giant viruses are widespread in the biosphere and play important roles in biogeochemical cycling and host genome evolution. Also known as nucleo-cytoplasmic large DNA viruses (NCLDVs), these eukaryotic viruses harbor the largest and most complex viral genomes known. Studies have shown that NCLDVs are frequently abundant in metagenomic datasets, and that sequences derived from these viruses can also be found endogenized in diverse eukaryotic genomes. The accurate detection of sequences derived from NCLDVs is therefore of great importance, but this task is challenging owing to both the high level of sequence divergence between NCLDV families and the extraordinarily high diversity of genes encoded in their genomes, including some encoding for metabolic or translation-related functions that are typically found only in cellular lineages. Here, we present ViralRecall, a bioinformatic tool for the identification of NCLDV signatures in ‘omic data. This tool leverages a library of giant virus orthologous groups (GVOGs) to identify sequences that bear signatures of NCLDVs. We demonstrate that this tool can effectively identify NCLDV sequences with high sensitivity and specificity. Moreover, we show that it can be useful both for removing contaminating sequences in metagenome-assembled viral genomes as well as the identification of eukaryotic genomic loci that derived from NCLDV. ViralRecall is written in Python 3.5 and is freely available on GitHub: https://github.com/faylward/viralrecall.