scholarly journals The Effects of Packaged, but Misguided, Single-Stranded DNA Genomes Are Transmitted to the Outer Surface of the øX174 Capsid

2021 ◽  
Author(s):  
Elizabeth T. Ogunbunmi ◽  
Aaron P. Roznowski ◽  
Bentley A. Fane
Keyword(s):  
Dna Binding ◽  
Outer Surface ◽  
Host Cells ◽  
Genome Packaging ◽  
Dna Viruses ◽  
Phosphate Backbone ◽  
J Proteins ◽  
Dna Organization ◽  
Icosahedral Viruses ◽  
Ssdna Viruses

Most icosahedral viruses condense their genomes into volumetrically constrained capsids. However, concurrent genome biosynthesis and packaging is specific to single-stranded (ss) DNA viruses. ssDNA genome packaging combines elements found in both double-stranded (ds) DNA and ssRNA systems. Similar to dsDNA viruses, the genome is packaged into a preformed capsid. Like ssRNA viruses, there are numerous capsid-genome associations. In ssDNA microviruses, the DNA binding protein J guides the genome between 60 icosahedrally ordered DNA binding pockets. It also partially neutralizes the DNA’s negative phosphate backbone. øX174-related microviruses, such as G4 and α3, have J proteins that differ in length and charge organization. This suggests that interchanging J proteins could alter the path used to guide DNA in the capsid. Previously, a øXG4J chimera, in which the øX174 J gene was replaced with the G4 gene, was characterized. It displayed lethal packaging defects, which resulted in procapsids being removed from productive assembly. Here, we report the characterization of another inviable chimera, øXα3J. Unlike øXG4J, øXα3J efficiently packaged DNA but produced non-infectious particles. These particles displayed a reduced ability to attach to host cells, suggesting internal DNA organization could distort the capsid’s outer surface. Mutations that restored viability altered J-coat protein contact sites. These results provide evidence that the organization of ssDNA can affect both packaging and post-packaging phenomena. Importance ssDNA viruses utilize icosahedrally ordered protein-nucleic acids interactions to guide and organize their genomes into preformed shells. As previously demonstrated, chaotic genome-capsid associations can inhibit øX174 packaging by destabilizing packaging complexes. However, the consequences of poorly organized genomes may extend beyond the packaging reaction. As demonstrated herein, it can lead to uninfectious packaged particles. Thus, ssDNA genomes should be considered an integral and structural virion component, affecting the properties of the entire particle, which includes the capsid’s outer surface.

scholarly journals Intercellular Transmission of Naked Viruses through Extracellular Vesicles: Focus on Polyomaviruses

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1086
Author(s):  
Francois Helle ◽  
Lynda Handala ◽  
Marine Bentz ◽  
Gilles Duverlie ◽  
Etienne Brochot
Keyword(s):  
Immune System ◽  
Extracellular Vesicles ◽  
Rna Viruses ◽  
Viral Transmission ◽  
Viral Fitness ◽  
Host Cells ◽  
Dna Viruses ◽  
Recent Advances ◽  
Viral Particles ◽  
Similar Strategy

Extracellular vesicles have recently emerged as a novel mode of viral transmission exploited by naked viruses to exit host cells through a nonlytic pathway. Extracellular vesicles can allow multiple viral particles to collectively traffic in and out of cells, thus enhancing the viral fitness and diversifying the transmission routes while evading the immune system. This has been shown for several RNA viruses that belong to the Picornaviridae, Hepeviridae, Reoviridae, and Caliciviridae families; however, recent studies also demonstrated that the BK and JC viruses, two DNA viruses that belong to the Polyomaviridae family, use a similar strategy. In this review, we provide an update on recent advances in understanding the mechanisms used by naked viruses to hijack extracellular vesicles, and we discuss the implications for the biology of polyomaviruses.

scholarly journals Adintoviruses: A Proposed Animal-Tropic Family of Midsize Eukaryotic Linear dsDNA (MELD) Viruses

2020 ◽  
Author(s):  
Gabriel J Starrett ◽  
Michael J Tisza ◽  
Nicole L Welch ◽  
Anna K Belford ◽  
Alberto Peretti ◽  
...  
Keyword(s):  
Genome Packaging ◽  
Metagenomic Sequence ◽  
Dna Viruses ◽  
Diverse Range ◽  
Integrase Gene ◽  
Data Mining Approach ◽  
Double Stranded Dna ◽  
Wide Range ◽  
Linear Dsdna ◽  
Dsdna Viruses

Abstract Polintons (also known as Mavericks) were initially identified as a widespread class of eukaryotic transposons named for their hallmark type B DNA polymerase and retrovirus-like integrase genes. It has since been recognized that many polintons encode possible capsid proteins and viral genome-packaging ATPases similar to those of a diverse range of double-stranded DNA (dsDNA) viruses. This supports the inference that at least some polintons are actually viruses capable of cell-to-cell spread. At present, there are no polinton-associated capsid protein genes annotated in public sequence databases. To rectify this deficiency, we used a data-mining approach to investigate the distribution and gene content of polinton-like elements and related DNA viruses in animal genomic and metagenomic sequence datasets. The results define a discrete family-like clade of viruses with two genus-level divisions. We propose the family name Adintoviridae, connoting similarities to adenovirus virion proteins and the presence of a retrovirus-like integrase gene. Although adintovirus-class PolB sequences were detected in datasets for fungi and various unicellular eukaryotes, sequences resembling adintovirus virion proteins and accessory genes appear to be restricted to animals. Degraded adintovirus sequences are endogenized into the germlines of a wide range of animals, including humans.

scholarly journals Diverse Functions of Polyamines in Virus Infection

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 628 ◽  
Author(s):  
Mason R. Firpo ◽  
Bryan C. Mounce
Keyword(s):  
Virus Infection ◽  
Mammalian Cells ◽  
Building Blocks ◽  
Host Cells ◽  
Genome Packaging ◽  
Bacteriophage Infection ◽  
Intracellular Parasites ◽  
Initial Work ◽  
Critical Resource ◽  
Positively Charged

As obligate intracellular parasites, viruses rely on host cells for the building blocks of progeny viruses. Metabolites such as amino acids, nucleotides, and lipids are central to viral proteins, genomes, and envelopes, and the availability of these molecules can restrict or promote infection. Polyamines, comprised of putrescine, spermidine, and spermine in mammalian cells, are also critical for virus infection. Polyamines are small, positively charged molecules that function in transcription, translation, and cell cycling. Initial work on the function of polyamines in bacteriophage infection illuminated these molecules as critical to virus infection. In the decades since early virus-polyamine descriptions, work on diverse viruses continues to highlight a role for polyamines in viral processes, including genome packaging and viral enzymatic activity. On the host side, polyamines function in the response to virus infection. Thus, viruses and hosts compete for polyamines, which are a critical resource for both. Pharmacologically targeting polyamines, tipping the balance to favor the host and restrict virus replication, holds significant promise as a broad-spectrum antiviral strategy.

Filamentous actin is required for lepidopteran nucleopolyhedrovirus progeny production

Microbiology ◽  
2000 ◽  
Vol 81 (7) ◽  
pp. 1881-1888 ◽  
Author(s):  
L. M. Kasman ◽  
L. E. Volkman
Keyword(s):  
Helicoverpa Zea ◽  
Virus Production ◽  
Host Cells ◽  
Actin Binding ◽  
Anticarsia Gemmatalis ◽  
Progeny Virus ◽  
Filamentous Actin ◽  
Phylogenetic Groups ◽  
Dna Viruses ◽  
Orgyia Pseudotsugata

Autographa californica M nucleopolyhedrovirus (AcMNPV) is the prototypical member of the Nucleopolyhedrosis genus of the Baculoviridae, a family of large, double-stranded DNA viruses that are highly diverse. Nucleocapsid morphogenesis of AcMNPV and others in the Nucleopolyhedrovirus genus takes place within the nuclei of infected host cells. Previously, we showed that filamentous actin (F-actin) is essential for this process to occur in AcMNPV-infected cells, an unprecedented finding for a DNA virus that replicates within the nucleus. Because of the fundamental importance of this requirement to our understanding of virus–host interactions, and because of the diversity of viruses included within the Nucleopolyhedrovirus genus, we were compelled to determine whether the replication of other nucleopolyhedroviruses was also F-actin dependent. We report here that progeny virus production of six other lepidopteran nucleopolyhedroviruses, representing both phylogenetic groups I and II within the genus, is also F-actin dependent. The six viruses studied (Spodoptera frugiperda MNPV, Bombyx mori NPV, Orgyia pseudotsugata MNPV, Lymantria dispar MNPV, Anticarsia gemmatalis MNPV and Helicoverpa zea SNPV) were unable to produce progeny in the presence of either cytochalasin D or latrunculin A, two actin-binding agents that interfere with F-actin-dependent processes but differ in their modes of action. F-actin-dependent progeny morphogenesis, therefore, appears to be a characteristic common among viruses in this genus that have lepidopteran hosts.

scholarly journals Virus–Host Coevolution with a Focus on Animal and Human DNA Viruses

2019 ◽  
Vol 88 (1) ◽  
pp. 41-56 ◽  
Author(s):  
Győző L. Kaján ◽  
Andor Doszpoly ◽  
Zoltán László Tarján ◽  
Márton Z. Vidovszky ◽  
Tibor Papp
Keyword(s):  
Life Form ◽  
Eukaryotic Cell ◽  
Arms Race ◽  
Host Cells ◽  
Dna Viruses ◽  
Fitness Level ◽  
Cellular Life ◽  
Human Dna ◽  
Insight Into

Abstract Viruses have been infecting their host cells since the dawn of life, and this extremely long-term coevolution gave rise to some surprising consequences for the entire tree of life. It is hypothesised that viruses might have contributed to the formation of the first cellular life form, or that even the eukaryotic cell nucleus originates from an infection by a coated virus. The continuous struggle between viruses and their hosts to maintain at least a constant fitness level led to the development of an unceasing arms race, where weapons are often shuttled between the participants. In this literature review we try to give a short insight into some general consequences or traits of virus–host coevolution, and after this we zoom in to the viral clades of adenoviruses, herpesviruses, nucleo-cytoplasmic large DNA viruses, polyomaviruses and, finally, circoviruses.

scholarly journals I(kappa)B(gamma) inhibits DNA binding of NF-kappaB p50 homodimers by interacting with residues that contact DNA.

1996 ◽  
Vol 16 (11) ◽  
pp. 6477-6485 ◽  
Author(s):  
S Bell ◽  
J R Matthews ◽  
E Jaffray ◽  
R T Hay
Keyword(s):  
Dna Binding ◽  
Binding Activity ◽  
Nf Kappa B ◽  
Protein Footprinting ◽  
I Kappa B Alpha ◽  
Dna Binding Activity ◽  
Cellular Genes ◽  
Phosphate Backbone ◽  
Nf Kappab ◽  
Contact Dna

NF-(kappa)B is an inducible transcription factor that activates many cellular genes involved in stress and immune response and whose DNA binding activity and cellular distribution are regulated by I(kappa)B inhibitor proteins. The interaction between NF-(kappa)B p50 and DNA was investigated by protein footprinting using chemical modification and partial proteolysis. Both methods confirmed lysine-DNA contacts already found in the crystal structure (K-147, K-149, K-244, K-275, and K-278) but also revealed an additional contact in the lysine cluster K-77-K-78-K-80 which was made on an extended DNA. Molecular modelling of such a DNA-protein complex revealed that lysine 80 is ideally placed to make phosphate backbone contacts in the extended DNA. Thus, it seems likely that the entire AB loop, containing lysines 77, 78, and 80, forms a C-shaped clamp that closes around the DNA recognition site. The same protein footprinting approaches were used to probe the interaction of p50 with the ankyrin repeat containing proteins I(kappa)B(gamma) and I(kappa)B(alpha). Lysine residues in p50 that were protected from modification by DNA were also protected from modification by I(kappa)B(gamma) but not I(kappa)B(alpha). Similarly, proteolytic cleavage at p50 residues which contact DNA was inhibited by bound I(kappa)B(gamma) but was enhanced by the presence of I(kappa)B(alpha). Thus, I(kappa)B(gamma) inhibits the DNA binding activity of p50 by direct interactions with residues contacting DNA, whereas the same residues remain exposed in the presence of I(kappa)B(alpha), which binds to p50 but does not block DNA binding.

scholarly journals Principles for enhancing virus capsid capacity and stability from a thermophilic virus capsid structure

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Nicholas P. Stone ◽  
Gabriel Demo ◽  
Emily Agnello ◽  
Brian A. Kelch
Keyword(s):  
Major Capsid Protein ◽  
Extreme Environment ◽  
Structural Basis ◽  
Genome Packaging ◽  
Virus Capsid ◽  
Dna Viruses ◽  
Double Stranded Dna ◽  
High Internal Pressure ◽  
Extracellular Environment ◽  
Catch Bonds

Abstract The capsids of double-stranded DNA viruses protect the viral genome from the harsh extracellular environment, while maintaining stability against the high internal pressure of packaged DNA. To elucidate how capsids maintain stability in an extreme environment, we use cryoelectron microscopy to determine the capsid structure of thermostable phage P74-26 to 2.8-Å resolution. We find P74-26 capsids exhibit an overall architecture very similar to those of other tailed bacteriophages, allowing us to directly compare structures to derive the structural basis for enhanced stability. Our structure reveals lasso-like interactions that appear to function like catch bonds. This architecture allows the capsid to expand during genome packaging, yet maintain structural stability. The P74-26 capsid has T = 7 geometry despite being twice as large as mesophilic homologs. Capsid capacity is increased with a larger, flatter major capsid protein. Given these results, we predict decreased icosahedral complexity (i.e. T ≤ 7) leads to a more stable capsid assembly.

scholarly journals Oligosaccharides as Receptors for JC Virus

2002 ◽  
Vol 76 (24) ◽  
pp. 12992-13000 ◽  
Author(s):  
Rika Komagome ◽  
Hirofumi Sawa ◽  
Takashi Suzuki ◽  
Yasuo Suzuki ◽  
Shinya Tanaka ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Demyelinating Disease ◽  
Jc Virus ◽  
Host Cells ◽  
Hemagglutination Activity ◽  
Dna Viruses ◽  
Double Stranded Dna ◽  
The Central Nervous System ◽  
Capsid Protein Vp1 ◽  
Sugar Chains

ABSTRACT JC virus (JCV) belongs to the polyomavirus family of double-stranded DNA viruses and in humans causes a demyelinating disease of the central nervous system, progressive multifocal leukoencephalopathy. Its hemagglutination activity and entry into host cells have been reported to depend on an N-linked glycoprotein containing sialic acid. In order to identify the receptors of JCV, we generated virus-like particles (VLP) consisting of major viral capsid protein VP1. We then developed an indirect VLP overlay assay to detect VLP binding to glycoproteins and a panel of glycolipids. We found that VLP bound to sialoglycoproteins, including α1-acid glycoprotein, fetuin, and transferrin receptor, and that this binding depended on α2-3-linked sialic acids and N-linked sugar chains. Neoglycoproteins were synthesized by using ovalbumin and conjugation with oligosaccharides containing the terminal α2-3- or α2-6-linked sialic acid or the branched α2-6-linked sialic acid. We show that the neoglycoprotein containing the terminal α2-6-linked sialic acid had the highest affinity for VLP, inhibited the hemagglutination activity of VLP and JCV, and inhibited the attachment of VLP to cells. We also demonstrate that VLP bound to specific glycolipids, such as lactosylceramide, and gangliosides, including GM3, GD2, GD3, GD1b, GT1b, and GQ1b, and that VLP bound weakly to GD1a but did not bind to GM1a, GM2, or galactocerebroside. Furthermore, the neoglycoprotein containing the terminal α2-6-linked sialic acid and the ganglioside GT1b inhibited JCV infection in the susceptible cell line IMR-32. These results suggest that the oligosaccharides of glycoproteins and glycolipids work as JCV receptors and may be feasible as anti-JCV agents.

scholarly journals DNA-Binding Activities of the HilC and HilD Virulence Regulatory Proteins of Salmonella enterica Serovar Typhimurium

2002 ◽  
Vol 184 (15) ◽  
pp. 4148-4160 ◽  
Author(s):  
Igor N. Olekhnovich ◽  
Robert J. Kadner
Keyword(s):  
Dna Binding ◽  
Salmonella Enterica ◽  
Mutational Analysis ◽  
Major Effect ◽  
Host Cells ◽  
Sequence Specificity ◽  
Sequence Alignments ◽  
Consensus Sequences ◽  
Serovar Typhimurium

ABSTRACT The HilC and HilD proteins of Salmonella enterica serovar Typhimurium are members of the AraC/XylS family of transcription regulators. They are encoded on Salmonella pathogenicity island 1 (SPI1) and control expression of the hilA gene, which encodes the major transcriptional activator for many genes encoded on SPI1 and elsewhere that contribute to invasion of host cells. Gel electrophoretic shift and DNase footprinting assays revealed that purified HilC and HilD proteins can bind to multiple regions in the hilA and hilC promoters and to a single region in the hilD promoter. Although both HilC and -D proteins can bind to the same DNA regions, they showed different dependencies on the sequence and lengths of their DNA targets. To identify the binding-sequence specificity of HilC and HilD, a series of single base substitutions changing each position in a DNA fragment corresponding to positions −92 to −52 of the hilC promoter was tested for binding to HilC and HilD in a gel shift DNA-binding assay. This mutational analysis in combination with sequence alignments allowed deduction of consensus sequences for binding of both proteins. The consensus sequences overlap but differ so that HilC can bind to both types of sites but HilD only to one. The hilA and hilC promoters contain multiple binding sites of each type, whereas the hilD promoter contains a site that binds HilC but not HilD without additional binding elements. The HilC and HilD proteins had no major effect on transcription from the hilA or hilD promoters using purified proteins in vitro but changed the choice of promoter at hilC. These results are consistent with a model derived from analysis of lacZ fusions stating that HilC and HilD enhance hilA expression by counteracting a repressing activity.

scholarly journals Comparative analysis of host-cell signalling mechanisms activated in response to infection with Rickettsia conorii and Rickettsia typhi

2007 ◽  
Vol 56 (7) ◽  
pp. 896-906 ◽  
Author(s):  
Elena Rydkina ◽  
Abha Sahni ◽  
David J. Silverman ◽  
Sanjeev K. Sahni
Keyword(s):  
Dna Binding ◽  
Host Cell ◽  
Spotted Fever ◽  
Binding Activity ◽  
Host Cells ◽  
Maximal Response ◽  
Rickettsia Conorii ◽  
P38 Kinase ◽  
Rickettsia Typhi ◽  
Dna Binding Activity

The Gram-negative intracellular bacteria Rickettsia conorii and Rickettsia typhi are the aetiological agents of Mediterranean spotted fever and endemic typhus, respectively, in humans. Infection of endothelial cells (ECs) lining vessel walls, and the resultant vascular inflammation and haemostatic alterations are salient pathogenetic features of both of these rickettsial diseases. An important consideration, however, is that dramatic differences in the intracellular motility and accumulation patterns for spotted fever versus typhus group rickettsiae have been documented, suggesting the possibility of unique and potentially different interactions with host cells. This study characterized and compared R. conorii- and R. typhi-mediated effects on cultured human ECs. The DNA-binding activity of nuclear transcription factor-κB (NF-κB) and the phosphorylation status of stress-activated p38 kinase were determined as indicators of NF-κB and p38 activation. R. conorii infection resulted in a biphasic activation of NF-κB, with an early increase in DNA-binding activity at 3 h, followed by a later peak at 24 h. The activated NF-κB species were composed mainly of RelA p65–p50 heterodimers and p50 homodimers. R. typhi infection of ECs resulted in only early activation of NF-κB at 3 h, composed primarily of p65–p50 heterodimers. Whilst R. conorii infection induced increased phosphorylation of p38 kinase (threefold mean induction) with the maximal response at 3 h, a considerably less-intense response peaking at about 6 h post-infection was found with R. typhi. Furthermore, mRNA expression of the chemokines interleukin (IL)-8 and monocyte chemoattractant protein-1 in ECs infected with either Rickettsia species was higher than the corresponding controls, but there were distinct differences in the secretion patterns for IL-8, suggesting the possibility of involvement of post-transcriptional control mechanisms or differences in the release from intracellular storage sites. Thus, the intensity and kinetics of host-cell responses triggered by spotted fever and typhus species exhibit distinct variations that could subsequently lead to differences in the extent of endothelial activation and inflammation and serve as important determinants of pathogenesis.

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