scholarly journals Suppression of a Subset of Interferon-Induced Genes by Human Papillomavirus Type 16 E7 via a Cyclin Dependent Kinase 8-Dependent Mechanism

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 311
Author(s):  
Sadie Rice ◽  
Seong-man Kim ◽  
Cynthia Rodriguez ◽  
William Songock ◽  
Gaurav Raikhy ◽  
...  
Keyword(s):  
Human Papillomaviruses ◽  
Type I ◽  
Viral Oncoprotein ◽  
Dna Viruses ◽  
Viral Genomes ◽  
Interferon Stimulated Genes ◽  
Human Papillomavirus Type 16 ◽  
Double Stranded Dna ◽  
Innate Immune Signaling ◽  
Episomal Maintenance

Persistent infection by human papillomaviruses (HPVs), small, double-stranded DNA viruses that infect keratinocytes of the squamous epithelia, can lead to the development of cervical and other cancers. The viral oncoprotein E7 contributes to viral persistence in part by regulating host gene expression through binding host transcriptional regulators, although mechanisms responsible for E7-mediated transcriptional regulation are incompletely understood. Type I IFN signaling promotes the expression of anti-viral genes, called interferon-stimulated genes (ISGs), through the phosphorylation and activation of STAT1. In this study, we have observed that the CR3 domain of E7 contributes to the episomal maintenance of viral genomes. Transcriptome analysis revealed that E7 transcriptionally suppresses a subset of ISGs but not through regulation of STAT1 activation. Instead, we discovered that E7 associates with Mediator kinase CDK8 and this is correlated with the recruitment of CDK8 to ISG promoters and reduced ISG expression. E7 fails to suppress ISGs in the absence of CDK8, indicating that CDK8 function contributes to the suppression of ISGs by E7. Altogether, E7/CDK8 association may be a novel mechanism by which E7 inhibits innate immune signaling.

scholarly journals Extrachromosomal Histone H2B Mediates Innate Antiviral Immune Responses Induced by Intracellular Double-Stranded DNA

2009 ◽  
Vol 84 (2) ◽  
pp. 822-832 ◽  
Author(s):  
Kouji Kobiyama ◽  
Fumihiko Takeshita ◽  
Nao Jounai ◽  
Asako Sakaue-Sawano ◽  
Atsushi Miyawaki ◽  
...  
Keyword(s):  
Immune Responses ◽  
Rna Virus ◽  
Cellular Signaling ◽  
Helical Structure ◽  
Human Cells ◽  
Type I Interferons ◽  
Type I ◽  
Histone H2b ◽  
Dna Viruses ◽  
Double Stranded Dna

ABSTRACT Fragments of double-stranded DNA (dsDNA) forming a right-handed helical structure (B-DNA) stimulate cells to produce type I interferons (IFNs). While an adaptor molecule, IFN-β promoter stimulator 1 (IPS-1), mediates dsDNA-induced cellular signaling in human cells, the underlying molecular mechanism is not fully understood. Here, we demonstrate that the extrachromosomal histone H2B mediates innate antiviral immune responses in human cells. H2B physically interacts with IPS-1 through the association with a newly identified adaptor, CIAO (COOH-terminal importin 9-related adaptor organizing histone H2B and IPS-1), to transmit the cellular signaling for dsDNA but not immunostimulatory RNA. Extrachromosomal histone H2B was biologically crucial for cell-autonomous responses to protect against multiplication of DNA viruses but not an RNA virus. Thus, the present findings provide evidence indicating that the extrachromosomal histone H2B is engaged in the signaling pathway initiated by dsDNA to trigger antiviral innate immune responses.

scholarly journals Baculovirus-inducing fast-acting innate immunity kills Plasmodium liver stages

2018 ◽  
Author(s):  
Talha Bin Emran ◽  
Mitsuhiro Iyori ◽  
Yuki Ono ◽  
Fitri Amelia ◽  
Yenni Yusuf ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Type I ◽  
Innate Immune Responses ◽  
Independent Manner ◽  
Liver Stage ◽  
Interferon Stimulated Genes ◽  
Rna Transcripts ◽  
Double Stranded Dna ◽  
Further Development

ABSTRACTBaculovirus (BV), an enveloped insect virus with a circular double-stranded DNA genome, possesses unique characteristics that induce strong innate immune responses in mammalian cells. Here, we show that BV administration not only sterilely protects BALB/c mice for at least 7 days from subsequent Plasmodium berghei sporozoite infection but also eliminates existing liver-stage parasites completely, effects superior to those of primaquine, and does so in a TLR9-independent manner. Six hours post-BV administration, IFN-α and IFN-γ were robustly produced in serum, and RNA transcripts of interferon-stimulated genes were drastically upregulated in the liver. The in vivo passive transfer of post-BV administration serum effectively eliminated liver-stage parasites, and IFN-α neutralization abolished this effect, indicating that the BV liver-stage parasite killing mechanism is downstream of the type I IFN signaling pathway. Our results demonstrate that BV is a potent IFN-inducing prophylactic and therapeutic agent with great potential for further development as a new malaria vaccine and/or anti-hypnozoite drug.

scholarly journals A pentameric protein ring with novel architecture is required for herpesviral packaging

2020 ◽  
Author(s):  
Allison L. Didychuk ◽  
Stephanie N. Gates ◽  
Matthew R. Gardner ◽  
Lisa M. Strong ◽  
Andreas Martin ◽  
...  
Keyword(s):  
Viral Genome ◽  
Molecular Motor ◽  
Dna Viruses ◽  
Dna Mutation ◽  
Viral Genomes ◽  
Barr Virus ◽  
Double Stranded Dna ◽  
Accessory Factor ◽  
Epstein Barr ◽  
Positively Charged

Genome packaging in large double-stranded DNA viruses requires a powerful molecular motor to force the viral genome into nascent capsids. This process appears mechanistically similar in two evolutionarily distant viruses, the herpesviruses and the tailed bacteriophages, which infect different kingdoms of life. While the motor and mechanism as a whole are thought to be conserved, accessory factors that influence packaging are divergent and poorly understood, despite their essential roles. An accessory factor required for herpesviral packaging is encoded by ORF68 in the oncogenic virus Kaposi’s sarcoma-associated herpesvirus (KSHV), whose homolog in Epstein Barr Virus (EBV) is BFLF1. Here, we present structures of both KSHV ORF68 and EBV BFLF1, revealing that these proteins form a highly similar homopentameric ring. The central channel of this ring is positively charged, and we demonstrate that this region of KSHV ORF68 binds double-stranded DNA. Mutation of individual positively charged residues within but not outside the channel ablates DNA binding, and in the context of KSHV infection these mutants fail to package the viral genome or produce progeny virions. Thus, we propose a model in which ORF68 facilitates the transfer of newly replicated viral genomes to the packaging motor.

scholarly journals Identification of Two Virus Integration Sites in the Brown Alga Feldmannia Chromosome

2007 ◽  
Vol 82 (3) ◽  
pp. 1407-1413 ◽  
Author(s):  
Russel H. Meints ◽  
Richard G. Ivey ◽  
Amy M. Lee ◽  
Tae-Jin Choi
Keyword(s):  
Vegetative Cells ◽  
Stem Loop ◽  
Dna Viruses ◽  
Viral Genomes ◽  
Virus Particles ◽  
Double Stranded Dna ◽  
Stem Loop Structure ◽  
Integration Sites ◽  
Virus Integration ◽  
Cg Dinucleotide

ABSTRACT Two similar, large double-stranded DNA viruses, Feldmannia species virus 158 (FsV-158) and FsV-178, replicate only in the unilocular reproductive cells (sporangia) of a brown filamentous alga in the genus Feldmannia. Virus particles are not present in vegetative cells but they are produced in the sporangia formed on vegetative filaments that have been transferred newly into culture. Thus, we proposed that these viruses exist in the vegetative cells in a latent form (R. G. Ivey, E. C. Henry, A. M. Lee, L. Klepper, S. K. Krueger, and R. H. Meints, Virology 220:267-273, 1996). In this article we present evidence that the two FsV genomes are integrated into the host genome during vegetative growth. The FsV genome integration sites were identified by cloning the regions where the FsV genome is linked to the host DNA. FsV-158 and FsV-178 are integrated into two distinct locations in the algal genome. In contrast, the integration sites in the two viral genomes are identical. Notably, the integration sites in the host and viruses contain GC and CG dinucleotide sequences, respectively, from which the GC sequences are recovered at both host-virus junctions. The splice sites in the two FsV genomes are predicted to form a stem-loop structure with the CG dinucleotide in the loop portion.

scholarly journals The logic of DNA replication in double-stranded DNA viruses: insights from global analysis of viral genomes

2016 ◽  
Vol 44 (10) ◽  
pp. 4551-4564 ◽  
Author(s):  
Darius Kazlauskas ◽  
Mart Krupovic ◽  
Česlovas Venclovas
Keyword(s):  
Dna Replication ◽  
Global Analysis ◽  
Dna Viruses ◽  
Viral Genomes ◽  
Double Stranded Dna

scholarly journals Genetic characteristics of human papillomavirus type 16, 18, 52 and 58 in southern China

2021 ◽  
Author(s):  
Yuee Zu ◽  
Zhihua Ou ◽  
Dan Wu ◽  
Wei Liu ◽  
Liwen Liu ◽  
...  
Keyword(s):  
Southern China ◽  
Human Papillomaviruses ◽  
Hunan Province ◽  
Strategy Development ◽  
Genetic Characteristics ◽  
Hpv Dna ◽  
Viral Genomes ◽  
Persistent Infections ◽  
Human Papillomavirus Type 16 ◽  
And Control

AbstractPersistent infections of high-risk human papillomaviruses (HPVs) are the leading cause of cervical cancers. We collected cervical exfoliated cell samples from females in Changsha city, Hunan Province and obtained 358 viral genomes of four major HPV types, including HPV 16 (n=82), 18 (n=35), 52 (n=121) and 58 (n=100). The lineage/sublineage distribution of the four HPVs confirmed previous epidemiological reports, with the predominant prevailing sublineage as A4 (50%), A1 (37%) and A3 (13%) for HPV16, A1 (83%) for HPV18, B2 (86%) for HPV52 and A1 (65%), A3 (19%) and A2 (12%) for HPV58. We also identified two potentially novel HPV18 sublineages, i.e. A6 and A7. Virus mutation analysis further revealed the presence of HPV16 and HPV58 strains associated with potentially high oncogenicity. These findings expanded our knowledge on the HPV genetic diversity in China, providing valuable evidence to facilitate HPV DNA screening, vaccine effectiveness evaluation and control strategy development.

scholarly journals All About the RNA: Interferon-Stimulated Genes That Interfere With Viral RNA Processes

2020 ◽  
Vol 11 ◽  
Author(s):  
Emily Yang ◽  
Melody M. H. Li
Keyword(s):  
Viral Replication ◽  
Rna Viruses ◽  
Rna Degradation ◽  
Viral Rna ◽  
Type I ◽  
E3 Ligases ◽  
Translation Inhibition ◽  
Viral Genomes ◽  
Interferon Stimulated Genes ◽  
Molecular Features

Interferon (IFN) signaling induces the expression of a wide array of genes, collectively referred to as IFN-stimulated genes (ISGs) that generally function to inhibit viral replication. RNA viruses are frequently targeted by ISGs through recognition of viral replicative intermediates and molecular features associated with viral genomes, or the lack of molecular features associated with host mRNAs. The ISGs reviewed here primarily inhibit viral replication in an RNA-centric manner, working to sense, degrade, or repress expression of viral RNA. This review focuses on dissecting how these ISGs exhibit multiple antiviral mechanisms, often through use of varied co-factors, highlighting the complexity of the type I IFN response. Specifically, these ISGs can mediate antiviral effects through viral RNA degradation, viral translation inhibition, or both. While the OAS/RNase L pathway globally degrades RNA and arrests translation, ISG20 and ZAP employ targeted RNA degradation and translation inhibition to block viral replication. Meanwhile, SHFL targets translation by inhibiting -1 ribosomal frameshifting, which is required by many RNA viruses. Finally, a number of E3 ligases inhibit viral transcription, an attractive antiviral target during the lifecycle of negative-sense RNA viruses which must transcribe their genome prior to translation. Through this review, we aim to provide an updated perspective on how these ISGs work together to form a complex network of antiviral arsenals targeting viral RNA processes.

scholarly journals Unique viruses that infect Archaea related to eukaryotes

2021 ◽  
Author(s):  
Ian Rambo ◽  
Valerie De Anda ◽  
Marguerite Langwig ◽  
Brett Baker
Keyword(s):  
Deep Sea ◽  
Structural Proteins ◽  
Genome Replication ◽  
Dna Viruses ◽  
Viral Genomes ◽  
Double Stranded Dna ◽  
Archaeal Viruses ◽  
Hydrothermal Sediments ◽  
Nucleocytoplasmic Large Dna Viruses ◽  
Globally Distributed

Abstract Asgard archaea are globally distributed, newly described microbes related to eukaryotes. Despite their importance, Asgard viruses have not been described. Here we characterize seven double-stranded DNA (dsDNA) viral genomes that infected Lokiarchaeota, Helarchaeota, and Thorarchaeota in deep-sea hydrothermal sediments. These viruses code for Caudovirales-like structural proteins, as well as proteins distinct from those described in archaeal viruses. They contain genes common in eukaryotic nucleocytoplasmic large DNA viruses (NCLDVs), and appear to be capable of semi-autonomous genome replication, repair, epigenetic modifications, and transcriptional regulation. Moreover, Helarchaeota viruses may hijack host ubiquitin systems similar to eukaryotic viruses. Recovery of these Asgard viral genomes reveals they contain features of both prokaryotic and eukaryotic viruses, and provides insights into their roles in the ecology and evolution of their hosts.

scholarly journals Functional Analysis of the Human Papillomavirus Type 16 E1∧E4 Protein Provides a Mechanism for In Vivo and In Vitro Keratin Filament Reorganization

2004 ◽  
Vol 78 (2) ◽  
pp. 821-833 ◽  
Author(s):  
Qian Wang ◽  
Heather Griffin ◽  
Shirley Southern ◽  
Deborah Jackson ◽  
Ana Martin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Human Papillomavirus ◽  
Intermediate Filament ◽  
Human Papillomaviruses ◽  
Intermediate Filament Protein ◽  
Type I ◽  
Human Papillomavirus Type 16 ◽  
Keratin 18

ABSTRACT High-risk human papillomaviruses, such as human papillomavirus type 16 (HPV16), are the primary cause of cervical cancer. The HPV16 E1∧E4 protein associates with keratin intermediate filaments and causes network collapse when expressed in epithelial cells in vitro. Here, we show that keratin association and network reorganization also occur in vivo in low-grade cervical neoplasia caused by HPV16. The 16E1∧E4 protein binds to keratins directly and interacts strongly with keratin 18, a member of the type I intermediate-filament family. By contrast, 16E1∧E4 bound only weakly to keratin 8, a type II intermediate-filament protein, and showed no detectable affinity for the type III protein, vimentin. The N-terminal 16 amino acids of the 16E1∧E4 protein, which contains the YPLLXLL motif that is conserved among supergroup A viruses, were sufficient to target green fluorescent protein to the keratin network. When expressed in the SiHa cervical epithelial cell line, the full-length 16E1∧E4 protein caused an almost total inhibition of keratin dynamics, despite the phosphorylation of keratin 18 at serine 33, which normally leads to 14-3-3-mediated keratin solubilization. Mutant 16E1∧E4 proteins which lack the LLKLL motif, or which have lost amino acids from their C termini, and which were compromised in the ability to associate with keratins did not disturb normal keratin dynamics. 16E1∧E4 was found to exist as dimers and hexamers, whereas a C-terminal deletion mutant (16E1∧E4Δ87-92) existed as monomers and formed multimeric structures only poorly. Considered together, our results suggest that by associating with keratins through its N terminus, and by associating with itself through its C terminus, 16E1∧E4 may act as a keratin cross-linker and prevent the movement of keratins between the soluble and insoluble compartments. The increase in avidity associated with multimeric binding may contribute to the ability of 16E1∧E4 to sequester its cellular targets in the cytoplasm.

scholarly journals Metagenomic compendium of 189,680 DNA viruses from the human gut microbiome

2021 ◽  
Author(s):  
Stephen Nayfach ◽  
David Páez-Espino ◽  
Lee Call ◽  
Soo Jen Low ◽  
Hila Sberro ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Target Genes ◽  
Human Gut ◽  
Dna Viruses ◽  
Viral Genomes ◽  
Human Gut Microbiome ◽  
Functional Potential ◽  
Double Stranded Dna ◽  
Reference Databases ◽  
Human Stool

AbstractBacteriophages have important roles in the ecology of the human gut microbiome but are under-represented in reference databases. To address this problem, we assembled the Metagenomic Gut Virus catalogue that comprises 189,680 viral genomes from 11,810 publicly available human stool metagenomes. Over 75% of genomes represent double-stranded DNA phages that infect members of the Bacteroidia and Clostridia classes. Based on sequence clustering we identified 54,118 candidate viral species, 92% of which were not found in existing databases. The Metagenomic Gut Virus catalogue improves detection of viruses in stool metagenomes and accounts for nearly 40% of CRISPR spacers found in human gut Bacteria and Archaea. We also produced a catalogue of 459,375 viral protein clusters to explore the functional potential of the gut virome. This revealed tens of thousands of diversity-generating retroelements, which use error-prone reverse transcription to mutate target genes and may be involved in the molecular arms race between phages and their bacterial hosts.

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