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Infection, Genetics and Evolution :... Jan 2018Viruses coevolve with their hosts to overcome host resistance and gain the upper hand in the evolutionary arms race. Drosophila innubila nudivirus (DiNV) is a double...
Viruses coevolve with their hosts to overcome host resistance and gain the upper hand in the evolutionary arms race. Drosophila innubila nudivirus (DiNV) is a double stranded DNA virus, closely related to Oryctes rhinoceros nudivirus (OrNV) and Kallithea virus. DiNV is the first DNA virus found to naturally infect Drosophila and therefore has the potential to be developed as a model for DNA virus immune defense and host/virus coevolution within its well-studied host system. Here we sequence and annotate the genome of DiNV and identify signatures of adaptation, revealing clues for genes involved in host-parasite coevolution. The circular genome is 155,555bp and contains 107 coding open reading frames (ORFs) and a wealth of AT-rich simple sequence repeats. While synteny is highly conserved between DiNV and Kallithea virus, it drops off rapidly as sequences become more divergent, consistent with rampant rearrangements across nudiviruses. Overall, we show that evolution of DiNV is likely due to adaptation of a very few genes coupled with high gene turnover.
Topics: Animals; Computational Biology; DNA Viruses; Drosophila; Evolution, Molecular; Genes, Viral; Genome, Viral; Host-Pathogen Interactions; Whole Genome Sequencing
PubMed: 29155284
DOI: 10.1016/j.meegid.2017.11.013 -
Viruses May 2021In a previous study, a metatranscriptomics survey of RNA viruses in several important lower vertebrate host groups revealed huge viral diversity, transforming the...
In a previous study, a metatranscriptomics survey of RNA viruses in several important lower vertebrate host groups revealed huge viral diversity, transforming the understanding of the evolution of vertebrate-associated RNA virus groups. However, the diversity of the DNA and retro-transcribing viruses in these host groups was left uncharacterized. Given that RNA sequencing is capable of revealing viruses undergoing active transcription and replication, we collected previously generated datasets associated with lower vertebrate hosts, and searched them for DNA and retro-transcribing viruses. Our results revealed the complete genome, or "core gene sets", of 18 vertebrate-associated DNA and retro-transcribing viruses in cartilaginous fishes, ray-finned fishes, and amphibians, many of which had high abundance levels, and some of which showed systemic infections in multiple organs, suggesting active transcription or acute infection within the host. Furthermore, these new findings recharacterized the evolutionary history in the families , , and , confirming long-term virus-host codivergence relationships for these virus groups. Collectively, our results revealed reliable and sufficient information within metatranscriptomics sequencing to characterize not only RNA viruses, but also DNA and retro-transcribing viruses, and therefore established a key methodology that will help us to understand the composition and evolution of the total "infectome" within a diverse range of vertebrate hosts.
Topics: Animals; Computational Biology; DNA Replication; DNA Viruses; Evolution, Molecular; Gene Expression Profiling; Gene Expression Regulation, Viral; Genome, Viral; High-Throughput Nucleotide Sequencing; Host-Pathogen Interactions; Metagenome; Metagenomics; Phylogeny; RNA Viruses; Retroviridae; Reverse Transcription; Sequence Analysis, RNA; Transcriptome; Vertebrates
PubMed: 34072878
DOI: 10.3390/v13061042 -
Virology Journal Apr 2023The genome of the largest known animal virus, the white spot syndrome virus (WSSV) responsible for huge economic losses and loss of employment in aquaculture, suffers...
BACKGROUND
The genome of the largest known animal virus, the white spot syndrome virus (WSSV) responsible for huge economic losses and loss of employment in aquaculture, suffers from inconsistent annotation nomenclature. Novel genome sequence, circular genome and variable genome length led to nomenclature inconsistencies. Since vast knowledge has already accumulated in the past two decades with inconsistent nomenclature, the insights gained on a genome could not be easily extendable to other genomes. Therefore, the present study aims to perform comparative genomics studies in WSSV on uniform nomenclature.
METHODS
We have combined the standard mummer tool with custom scripts to develop missing regions finder (MRF) that documents the missing genome regions and coding sequences in virus genomes in comparison to a reference genome and in its annotation nomenclature. The procedure was implemented as web tool and in command-line interface. Using MRF, we have documented the missing coding sequences in WSSV and explored their role in virulence through application of phylogenomics, machine learning models and homologous genes.
RESULTS
We have tabulated and depicted the missing genome regions, missing coding sequences and deletion hotspots in WSSV on a common annotation nomenclature and attempted to link them to virus virulence. It was observed that the ubiquitination, transcription regulation and nucleotide metabolism might be essentially required for WSSV pathogenesis; and the structural proteins, VP19, VP26 and VP28 are essential for virus assembly. Few minor structural proteins in WSSV would act as envelope glycoproteins. We have also demonstrated the advantage of MRF in providing detailed graphic/tabular output in less time and also in handling of low-complexity, repeat-rich and highly similar regions of the genomes using other virus cases.
CONCLUSIONS
Pathogenic virus research benefits from tools that could directly indicate the missing genomic regions and coding sequences between isolates/strains. In virus research, the analyses performed in this study provides an advancement to find the differences between genomes and to quickly identify the important coding sequences/genomes that require early attention from researchers. To conclude, the approach implemented in MRF complements similarity-based tools in comparative genomics involving large, highly-similar, length-varying and/or inconsistently annotated viral genomes.
Topics: Animals; DNA Viruses; Viruses; Genome, Viral; Genomics; White spot syndrome virus 1
PubMed: 37072853
DOI: 10.1186/s12985-023-02035-w -
Annual Review of Virology Nov 2015Translocation of viral double-stranded DNA (dsDNA) into the icosahedral prohead shell is catalyzed by TerL, a motor protein that has ATPase, endonuclease, and... (Review)
Review
Translocation of viral double-stranded DNA (dsDNA) into the icosahedral prohead shell is catalyzed by TerL, a motor protein that has ATPase, endonuclease, and translocase activities. TerL, following endonucleolytic cleavage of immature viral DNA concatemer recognized by TerS, assembles into a pentameric ring motor on the prohead's portal vertex and uses ATP hydrolysis energy for DNA translocation. TerL's N-terminal ATPase is connected by a hinge to the C-terminal endonuclease. Inchworm models propose that modest domain motions accompanying ATP hydrolysis are amplified, through changes in electrostatic interactions, into larger movements of the C-terminal domain bound to DNA. In phage ϕ29, four of the five TerL subunits sequentially hydrolyze ATP, each powering translocation of 2.5 bp. After one viral genome is encapsidated, the internal pressure signals termination of packaging and ejection of the motor. Current focus is on the structures of packaging complexes and the dynamics of TerL during DNA packaging, endonuclease regulation, and motor mechanics.
Topics: DNA Packaging; DNA Viruses; DNA, Viral; Viral Proteins; Virus Assembly
PubMed: 26958920
DOI: 10.1146/annurev-virology-100114-055212 -
Communications Biology May 2022The DNA sensor cGAS detects cytosolic DNA and instigates type I interferon (IFN) expression. Recent studies find that cGAS also localizes in the nucleus and binds the...
The DNA sensor cGAS detects cytosolic DNA and instigates type I interferon (IFN) expression. Recent studies find that cGAS also localizes in the nucleus and binds the chromatin. Despite the mechanism controlling nuclear cGAS activation is well elucidated, whether nuclear cGAS participates in DNA sensing is unclear. Here, we report that herpes simplex virus 1 (HSV-1) infection caused the release of cGAS from the chromatin into the nuclear soluble fraction. Like its cytosolic counterpart, the leaked nuclear soluble cGAS also sensed viral DNA, produced cGAMP, and induced mRNA expression of type I IFN and interferon-stimulated genes. Consistently, the nuclear soluble cGAS limited HSV-1 infection. Furthermore, enzyme-deficient mutation (D307A) or cGAS inhibitor RU.251 abolished nuclear cGAS-mediated innate immune responses, suggesting that enzymatic activity is also required for nuclear soluble cGAS. Taken all together, our study demonstrates that nuclear soluble cGAS acts as a nuclear DNA sensor detecting nuclear-replicating DNA viruses.
Topics: Chromatin; DNA; DNA Virus Infections; DNA Viruses; Herpes Simplex; Humans; Nucleotidyltransferases
PubMed: 35538147
DOI: 10.1038/s42003-022-03400-1 -
Archives of Virology Dec 2017Viruses enter host cells via several mechanisms, including endocytosis, macropinocytosis, and phagocytosis. They can also fuse at the plasma membrane and can spread... (Comparative Study)
Comparative Study Review
Viruses enter host cells via several mechanisms, including endocytosis, macropinocytosis, and phagocytosis. They can also fuse at the plasma membrane and can spread within the host via cell-to-cell fusion or syncytia. The mechanism used by a given viral strain depends on its external topology and proteome and the type of cell being entered. This comparative review discusses the cellular attachment receptors and entry pathways of dsDNA viruses belonging to the families Adenoviridae, Baculoviridae, Herpesviridae and nucleocytoplasmic large DNA viruses (NCLDVs) belonging to the families Ascoviridae, Asfarviridae, Iridoviridae, Phycodnaviridae, and Poxviridae, and giant viruses belonging to the families Mimiviridae and Marseilleviridae as well as the proposed families Pandoraviridae and Pithoviridae. Although these viruses have several common features (e.g., topology, replication and protein sequence similarities) they utilize different entry pathways to infect wide-range of hosts, including humans, other mammals, invertebrates, fish, protozoa and algae. Similarities and differences between the entry methods used by these virus families are highlighted, with particular emphasis on viral topology and proteins that mediate viral attachment and entry. Cell types that are frequently used to study viral entry are also reviewed, along with other factors that affect virus-host cell interactions.
Topics: Animals; DNA Virus Infections; DNA Viruses; Humans; Virus Attachment; Virus Internalization
PubMed: 28866775
DOI: 10.1007/s00705-017-3497-8 -
Microbiology Spectrum Dec 2022The CRESS-DNA viruses are the ubiquitous virus detected in almost all eukaryotic life trees and play an essential role in the maintaining ecosystem of the globe. Still,...
The CRESS-DNA viruses are the ubiquitous virus detected in almost all eukaryotic life trees and play an essential role in the maintaining ecosystem of the globe. Still, their genetic diversity is not fully understood. Here, we bring to light the genetic diversity of replication (Rep) and capsid (Cap) proteins of CRESS-DNA viruses. We divided the Rep protein of the CRESS-DNA virus into 10 clusters using CLANS and phylogenetic analyses. Also, most of the Rep protein in Rep cluster 1 (R1) and R2 (, , , and CRESSV1-5) contain the Viral_Rep superfamily and P-loop_NTPase superfamily domains, while the Rep protein of viruses in other clusters has no such characterized functional domain. The , , and CRESSV1-3 viruses contain two domains, such as Viral_Rep and P-loop_NTPase; the CRESSV4 and CRESSV5 viruses have only the Viral_Rep domain; most of the sequences in the pCRESS-related group have only P-loop_NTPase; and do not have these two domains. Further, we divided the Cap protein of the CRESS-DNA virus into 20 clusters using CLANS and phylogenetic analyses. The Rep and Cap proteins of and are grouped into a specific cluster. Cap protein of CRESS-DNA viruses grouped with one cluster and Rep protein with another cluster. Further, our study reveals that selection pressure plays a significant role in the evolution of CRESS-DNA viruses' Rep and Cap genes rather than mutational pressure. We hope this study will help determine the genetic diversity of CRESS-DNA viruses as more sequences are discovered in the future. The genetic diversity of CRESS-DNA viruses is not fully understood. CRESS-DNA viruses are classified as CRESSV1 to CRESSV6 using only Rep protein. This study revealed that the Rep protein of the CRESS-DNA viruses is classified as CRESSV1 to CRESSV6 groups and the new Smacoviridae-related, CRESSV2-related, pCRESS-related, Circoviridae-related, and 1 to 4 outgroups, according to the Viral_Rep and P-loop_NTPase domain organization, CLANS, and phylogenetic analysis. Furthermore, for the first time in this study, the Cap protein of CRESS-DNA viruses was classified into 20 distinct clusters by CLANS and phylogenetic analysis. Through this classification, the genetic diversity of CRESS-DNA viruses clarifies the possibility of recombinations in Cap and Rep proteins. Finally, it has been shown that selection pressure plays a significant role in the evolution and genetic diversity of Cap and Rep proteins. This study explains the genetic diversity of CRESS-DNA viruses and hopes that it will help classify future detected viruses.
Topics: DNA, Viral; Phylogeny; Brassicaceae; Ecosystem; Nucleoside-Triphosphatase; DNA Viruses; Capsid Proteins; Genetic Variation; Genome, Viral; DNA, Circular
PubMed: 36346238
DOI: 10.1128/spectrum.01057-22 -
Virology Oct 2014Genome encapsidation is an essential step in the life cycle of viruses. Viruses either use some of the most powerful ATP-dependent motors to compel the genetic material... (Review)
Review
Genome encapsidation is an essential step in the life cycle of viruses. Viruses either use some of the most powerful ATP-dependent motors to compel the genetic material into the preformed capsid or make use of the positively charged proteins to bind and condense the negatively charged genome in an energy-independent manner. While the former is a hallmark of large DNA viruses, the latter is commonly seen in small DNA and RNA viruses. Discoveries of many complex giant viruses such as mimivirus, megavirus, pandoravirus, etc., belonging to the nucleo-cytoplasmic large DNA virus (NCLDV) superfamily have changed the perception of genome packaging in viruses. From what little we have understood so far, it seems that the genome packaging mechanism in NCLDVs has nothing in common with other well-characterized viral packaging systems such as the portal-terminase system or the energy-independent system. Recent findings suggest that in giant viruses, the genome segregation and packaging processes are more intricately coupled than those of other viral systems. Interestingly, giant viral packaging systems also seem to possess features that are analogous to bacterial and archaeal chromosome segregation. Although there is a lot of diversity in terms of host range, type of genome, and genome size among viruses, they all seem to use three major types of independent innovations to accomplish genome encapsidation. Here, we have made an attempt to comprehensively review all the known viral genome packaging systems, including the one that is operative in giant viruses, by proposing a simple and expanded classification system that divides the viral packaging systems into three large groups (types I-III) on the basis of the mechanism employed and the relatedness of the major packaging proteins. Known variants within each group have been further classified into subgroups to reflect their unique adaptations.
Topics: DNA Packaging; DNA Viruses; DNA, Viral; Genome, Viral; Models, Biological; Virus Assembly
PubMed: 24998349
DOI: 10.1016/j.virol.2014.06.022 -
The Journal of Experimental Medicine Apr 2017Stimulator of IFN genes (STING) is a central adaptor protein that mediates the innate immune responses to DNA virus infection. Although ubiquitination is essential for...
Stimulator of IFN genes (STING) is a central adaptor protein that mediates the innate immune responses to DNA virus infection. Although ubiquitination is essential for STING function, how the ubiquitination/deubiquitination system is regulated by virus infection to control STING activity remains unknown. In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1 infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. Inhibition of p38 MAPK enhanced the production of IFNs in response to virus infection and protected mice from lethal HSV-1 infection. Thus, our study reveals a critical role of p38-mediated USP21 phosphorylation in regulating STING-mediated antiviral functions and identifies p38-USP21 axis as an important pathway that DNA virus adopts to avoid innate immunity responses.
Topics: Animals; Chlorocebus aethiops; DNA Viruses; HEK293 Cells; Humans; Immunity, Innate; Interferon Regulatory Factor-3; Interferon Type I; Membrane Proteins; Mice; Phosphorylation; Ubiquitin Thiolesterase; Vero Cells; p38 Mitogen-Activated Protein Kinases
PubMed: 28254948
DOI: 10.1084/jem.20161387 -
Advances in Virus Research 2020Nucleocytoviricota viruses (NCVs) belong to a newly established phylum originally grouped as Nucleocytoplasmic large DNA viruses. NCVs are unique because of their large... (Review)
Review
Nucleocytoviricota viruses (NCVs) belong to a newly established phylum originally grouped as Nucleocytoplasmic large DNA viruses. NCVs are unique because of their large and complicated genomes that contain cellular genes with homologs from all kingdoms of life, raising intensive debates on their evolutional origins. Many NCVs pack their genomes inside massive icosahedral capsids assembled from thousands of proteins. Studying the assembly mechanism of such capsids has been challenging until breakthroughs from structural studies. Subsequently, several models of the capsid assembly were proposed, which provided some interesting insights on this elaborate process. In this review, we discuss three of the most recent assembly models as well as supporting experimental observations. Furthermore, we propose a new model that combines research developments from multiple sources. Investigation of the assembly process of these vast NCV capsids will facilitate future deciphering of the molecular mechanisms driving the formation of similar supramolecular complexes.
Topics: Books; Capsid; Capsid Proteins; DNA Viruses; Genome, Viral; Models, Molecular; Virus Assembly
PubMed: 33837719
DOI: 10.1016/bs.aivir.2020.09.006