Long distance virus classification

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Tan Z. Predicting the antigenic variant of human influenza A H3N2 virus with a stacked auto-encoder model. Lapedes A. The geometry of shape space: application to influenza. Journal of Theoretical Biology. Archetti I. Persistent antigenic variation of influenza A viruses after incomplete neutralization in ovo with heterologous immune serum. Burnet F. The action of certain surface-active agents on viruses.

Smith D. Mapping the antigenic and genetic evolution of influenza virus. Bedford T. Integrating influenza antigenic dynamics with molecular evolution. Mapping of H3N2 influenza antigenic evolution in China reveals a strategy for vaccine strain recommendation. Nature Communications. Lin K. Amino acid encoding schemes from protein structure alignments: multi-dimensional vectors to describe residue types. Wilson I. Because the helical structure can continue indefinitely, there are also no constraints on how much nucleic acid can be packaged into the virion: the capsid length will be the size of the coiled nucleic acid.

Helical viruses can be enveloped or naked. The first virus described, tobacco mosaic virus, is a naked helical virus. In fact, most plant viruses are helical, and it is very uncommon that a helical plant virus is enveloped.

In contrast, all helical animal viruses are enveloped. These include well-known viruses such as influenza virus, measles virus, mumps virus, rabies virus, and Ebola virus Fig. A Vesicular stomatitis virus forms bullet-shaped helical nucleocapsids. Fred A. B Tobacco mosaic virus forms long helical tubes. C The helical Ebola virus forms long threads that can extend over nm in length. Of the two major capsid structures, the icosahedron is by far more prevalent than the helical architecture.

In comparison to a helical virus where the capsid proteins wind around the nucleic acid, the genomes of icosahedral viruses are packaged completely within an icosahedral capsid that acts as a protein shell. Initially these viruses were thought to be spherical, but advances in electron microscopy and X-ray crystallography revealed these were actually icosahedral in structure.

An icosahedron is a geometric shape with 20 sides or faces , each composed of an equilateral triangle. An icosahedron has what is referred to as 2—3—5 symmetry , which is used to describe the possible ways that an icosahedron can rotate around an axis. If you hold an icosahedral die in your hand, you will notice there are different ways of rotating it Fig. A helix is mathematically defined by two parameters, the amplitude and the pitch, that are also applied to helical capsid structures.

The amplitude is simply the diameter of the helix and tells us the width of the capsid. The pitch is the height or distance of one complete turn of the helix. In the same way that we can determine the height of a one-story staircase by adding up the height of the stairs, we can figure out the pitch of the helix by determining the rise , or distance gained by each capsid subunit.

A staircase with 20 stairs that are each 6 inches tall results in a staircase of 10 feet in height; a virus with This is the architecture of tobacco mosaic virus.

Your pencil would be right in the middle of a triangle facing up and a triangle facing down. If you rotate the icosahedron clockwise, you will find that in degrees you encounter the same arrangement symmetry : a triangle facing up and a triangle facing down. Continuing to rotate the icosahedron brings you back to where you began. This is known as the twofold axis of symmetry, because as you rotate the shape along this axis your pencil , you encounter your starting structure twice in one revolution: once when you begin, and again when rotated degrees.

On the other hand, if you put your pencil axis directly through the center one of the small triangle faces of the icosahedron, you will encounter the initial view two additional times as you rotate the shape, for a total of three times. This is the threefold axis. Similarly, if your pencil axis goes through a vertex or tip of the icosahedron, you will find symmetry five times in one rotation, forming the fivefold axis. It is for this reason that an icosahedron is known to have 2—3—5 symmetry, because it has twofold, threefold, and fivefold axes of symmetry.

This terminology is useful when dealing with an icosahedral virus because it can be used to indicate specific locations on the virus or where the virion has interactions with the cell surface. For instance, if a virus interacts with a cell surface receptor at the threefold axis, then you know this interaction occurs at one of the faces of the icosahedron.

A protein protruding from the capsid at the fivefold axis will be found at one of the vertices tips of the icosahedron. All of the illustrations of viruses in Fig. How many twofold axes of symmetry are found in one icosahedron? How about the number of threefold or fivefold axes? How many faces, edges, and vertices are found in an icosahedron? A Icosahedron faces fuchsia triangles , edges red rectangles , and vertices violet pentagons are indicated on the white icosahedron.

B The twofold axis of symmetry occurs when the axis is placed through the center of an edge. The threefold axis occurs when the axis is placed in the center of a face C , and the fivefold axis passes through a vertex of the icosahedron D. Viral proteins form each face small triangle of the icosahedral capsid.

Viral proteins are not triangular, however, and so one protein subunit alone is not sufficient to form the entire face. Therefore, a face is formed from at least three viral protein subunits fitted together Fig. These can all be the same protein, or they can be three different proteins. The subunits together form what is called the structural unit. The structural unit repeats to form the capsid of the virion. A Virus capsids are composed of viral protein subunits that form structural units.

The triangulation number T indicates the number of structural units per face of the icosahedron. The red lines outline a triangular face of the icosahedron, while the purple pentagons indicate the vertices fivefold axes of the icosahedron.

But how can some viruses form very large icosahedral capsids? The answer is repetition. The structural unit can be repeated over and over again to form a larger icosahedron side. The number of structural units that creates each side is called the triangulation number T , because the structural units form the triangle face of the icosahedron.

The geometry and math involved with icosahedral capsid structure can be complex, and only the very basics are described here. In any case, by increasing the number of identical structural units on each face, the icosahedron can become progressively larger without requiring additional novel proteins to be produced. Some viruses have triangulation numbers over 25, even! The proteins that compose the structural unit may form three dimensional structures known as capsomeres that are visible in an electron micrograph.

In icosahedral viruses, capsomeres generally take the form of pentons containing five units or hexons containing six units that form a visible pattern on the surface of the icosahedron See Fig. Capsomeres are morphological units that arise from the interaction of the proteins within the repeated structural units.

Why does the icosahedral virus structure appear so often? Research has shown that proteins forming icosahedral symmetry require lesser amounts of energy, compared to other structures, and so this structure is evolutionarily favored. Many viruses that infect animals are icosahedral, including human papillomavirus, rhinovirus, hepatitis B virus, and herpesviruses Fig. Like their helical counterparts, icosahedral viruses can be naked or enveloped, as well.

Poliovirus A , rotavirus B , varicella—zoster virus C , the virus that causes chickenpox and shingles, and reovirus D. Note that C is enveloped. The majority of viruses can be categorized as having helical or icosahedral structure. A few viruses, however, have a complex architecture that does not strictly conform to a simple helical or icosahedral shape.

Poxviruses, geminiviruses, and many bacteriophages are examples of viruses with complex structure Fig. Poxviruses, including the viruses that cause smallpox or cowpox, are large oval or brick-shaped particles — nm long. Price and P.

These deletion variants were created via PCR amplification of pF1 by using forward primer and reverse primers , , , , and , respectively, and by ligating the products into pF1 fs via common Hin dIII and Msc I sites. Ball, University of Alabama. The second-round PCR product was produced by mutually primed extension of first-round PCR products generated with forward primer and reverse primer or forward primer and reverse primer by using pF1 as a template.

The resulting products were extended by mutual priming and amplification with primers and and then cloned into pBDL10 via common Age I and Sph I sites.

The resulting products were mutually extended and amplified by using primers and and cloned into pRS 14 via common Sst I and Xho I sites. RNAs were electrophoresed through gels containing 1. Four days postinduction, yeast cells were diluted to 1. Approximately 1. For some experiments, cells were subjected to a second round of sorting and regrowth, with similar results. To study cis -acting functions of RNA1 replicons independently of their protein-coding potential, protein A must be provided in trans.

Slower-migrating forms of Pariacoto virus RNA1 and RNA2 have been tentatively identified as covalently linked head-to-tail concatemers Alternatively, the slower-migrating RNA3 band we observe could be a double-stranded form that remained undenatured since i it comigrates with double-stranded RNA3 created by annealing synthetic negative- and positive-strand RNA3 transcripts in high salt, ii strand-specific Northern blotting results indicate that the amounts of negative- and positive-strand RNAs in this band are equivalent, and iii this product can be gel purified and separated into products that coelectrophorese with single-strand RNA3 after further denaturation data not shown.

A very low level of polyadenylated protein A mRNA, transcribed from pFA, could be detected on longer exposures of positive-strand blots. Accordingly, pFA was used as a helper plasmid in all testing described below. The design of these deletion constructs, their average relative levels of RNA1 and RNA3 positive strand accumulation, and a representative Northern blot are presented in Fig.

All deletion derivatives were tested multiple times, and similar results were also obtained by using negative-strand probes data not shown. Thus, sequences immediately downstream of nt were important for RNA3 production.

A Constructs used to map cis -acting replication elements in RNA1. The RNA1 frameshift derivative is illustrated at the top, as in Fig. Regions that are present thick bars or absent thin lines in several deletion constructs are illustrated below. To the right of each construct are the average levels of RNA1 and RNA3 positive-strand accumulation, normalized to that of pF1 fs , determined from three independent experiments.

Together these data suggest that sequences controlling efficient RNA3 production lie between nt and , which we term the proximal subgenomic control element PSCE. However, a subset of this region, nt to , could support a low level of RNA3 production.

Because both duplications encompassed the entire RNA3 region, the resultant constructs were referred to as double subgenomics. Both double-subgenomic constructs replicated in cis to levels comparable to that for wild-type RNA1 Fig. Consistent with the above deletion analysis, expression of subgenome length RNA3 by pF1ds1 suggested that the functional local sequence element directing basal RNA3 expression was contained within nt to Similar results were observed for triple-subgenomic RNA1 derivatives data not shown.

Polarity effects on initiation site preference have also been described for other positive-strand RNA virus genomes expressing multiple subgenomic mRNAs 17 , 29 , 32 , Double-subgenomic constructs and RNA3-based vector design. A The designs of double-subgenomic constructs are illustrated as in Fig. C Fluorescence profiles collected from 10 4 yeast cells that had been cotransformed with pF1 fs dsGFP and an empty vector top or pFA bottom.

It has been shown previously that a synthetic gene encoding GFP can be inserted in RNA3 and expressed in a replication-dependent manner Based on their design, the double-subgenomic constructs of Fig.

Therefore this construct was created in the context of trans -replicating replicon pF1 fs. This reduction can be explained in part by the reduced levels of RNA accumulation observed for replication in trans Fig. In the absence of protein A, only a basal level of fluorescence was detected, which was typical for yeast lacking any GFP sequences.

The dim population probably represents cells that recently lost one or both FHV expression plasmids, as plasmids segregate unequally in yeast 12 , 14 , 36 , During our studies with deletion mutants, it became apparent that a region 1. Dasgupta, personal communication containing deletions of nt to and to As previously described for trans replication in mammalian cells, a similar derivative replicated to high levels and expressed normal levels of RNA3 9.

Thus, the region between nt and contains a determinant for RNA3 production. Mapping of a distal region involved in RNA3 accumulation. Dashes, deleted sequences. Note that some constructs from panel A are also shown for reference. Open rectangle, location of the core DSCE. Finer mapping Fig. This suggested that residues between and were needed for RNA3 production. At a finer scale Fig. Additional constructs were created in order to delineate the minimal distal element controlling RNA3 production.

Thus, a small distal element, centered on an nt core, was shown to be necessary for RNA3 production. We refer to this as the distal subgenomic control element DSCE. To explore how such a short, distal sequence element might exert its effect on subgenome production from 1. Computer-assisted prediction of the lowest-free-energy secondary structure of positive-strand RNA1 Fig. The proximity of helix 1 to the RNA3 start site at position was interesting.

Although nt to are located far from the subgenomic region in the primary sequence, the predicted RNA1 secondary structure places both helices near the subgenomic start site. This prediction also included values for pnum, the number of base pairing alternatives, to estimate the confidence level for a given base's predicted structure Although the DSCE had high pnum values, indicating that these residues could base pair with many alternate partners, 7 of the top 10 RNA1 structure predictions i.

Furthermore, 9 of the top 10 predictions had the same structure for residues to Potential base pairing of the DSCE to regions proximal to the subgenomic region start site. The intRE is bracketed. Gray box, region around the subgenomic region start site. Bottom Magnification of the region contained within the gray box. Putative helices 1 and 2 are bracketed. Arrow, RNA3 start site at nt Both mutations completely abolished both positive- and negative-strand RNA3 accumulation Fig.

Interestingly, these mutations also led to increased RNA1 accumulation see Discussion. Combining the two mutations, which restored base pairing potential in pF1 fs mut3 Fig. However, RNA production was restored Fig. Mutated nucleotides affecting these potential base pairing interactions are in boldface. This band is visible in longer exposures of the plus strand blot.

However, this approach was limited to only those mutations that were chosen for analysis. To encompass all possible variations in a relevant sequence, we used a randomization and in vivo selection approach.

An additional construct, pF1 fs dsGFPran3, was similar to pF1 fs dsGFPran1 but contained a smaller subset of sequences represented in the DSCE; it was randomized in such a way as to prevent the wild-type sequence from re-forming in the population Fig.

These plasmids were transformed into yeast expressing protein A from a chromosomally integrated form of pFA. Following induction of FHV replication, cells were analyzed on a fluorescence-activated cell sorter. As described for Fig. These data indicated that the pF1 fs dsGFPran1 and pF1 fs dsGFPran2 populations contained a small number of cells that expressed GFP, and bright cells were collected from them by sorting and expanded in culture for analysis.

In vivo selection of GFP-expressing replicons. B Cell fluorescence versus forward scattering FSC , as plotted for 10 4 cells of the indicated cultures. The gates used for cell sorting and percentages of the total within these bounds are shown.

D Msc I digestion of pF1 fs dsGFP or the indicated pF1 fs dsGFPran1 plasmid pools: library, original plasmid library prior to yeast transformation; unsorted, plasmids after recovery from an unsorted yeast population; sorted, plasmids after recovery from a yeast population sorted as for panel B.

These results confirm the lack of GFP expression for these constructs Fig. Thus, fluorescence-based sorting had selectively enriched for those cells in the original population that expressed RNA3L. Digestion of pF1 fs dsGFP with this enzyme yielded the expected products of 8,, 1,, and bp Fig.

Digestion of the original pF1 fs dsGFPran1 library before or after recovery from unsorted yeast gave rise to products of 10, and bp, which is consistent with the virtual elimination of the Msc I site in the DSCE region from the plasmid pool.

In contrast, band intensities indicate that about one-half of the plasmid pool rescued from the sorted pF1 fs dsGFPran1 population regained the wild-type restriction pattern, implying that the previously randomized positions in these plasmids were now enriched for sequence TGGCCA. Both unsorted populations contained relatively even distributions of sequences at the randomized positions, although a slight bias for T or G was present at all positions, perhaps due to inefficient mixing of deoxynucleoside phosphoramidites during oligonucleotide synthesis.

After the pF1 fs dsGFPran1 population was sorted, a strong bias for consensus sequence TGGCCA emerged at the randomized positions, thus restoring base pairing potential, and 46 of 91 plasmids contained the canonical Msc I restriction site.

The other clones contained sequences in these positions that clustered around this consensus sequence but that also contained some mismatch. Some plasmids also contained the consensus sequence, but the sequence was shifted slightly from its normal position e.

To determine whether clones containing sequences other than TGGCCA at nt to could confer RNA3-directed GFP expression, these plasmids were individually tested by retransforming them back into protein A-expressing yeast, inducing FHV replication with galactose, and analyzing them by flow cytometry. Of 45 clones tested, 40 yielded cells with bright fluorescence, indicating that helix 2 can tolerate some level of mismatch, while 5 clones yielded cells with little or no fluorescence.

These nonexpressing clones could have been derived from cells that were spuriously scored positive during the sorting procedure, as for pF1 fs dsGFPmut4 Fig. RNA2 replication requires RNA1 replication in trans 9 , although the basis for this requirement is unknown. However, this effect was not seen in repeats of this experiment. With increasing trade and movement of agricultural commodities it is inevitable that ssDNA viruses move across continents.

Emergence of ToLCNDV in Europe and spread of TYLCV spreading through Caribbean island into central and North America, the new world squash leaf curl virus affecting cucurbit production in Asia Minor are some examples to cite how plant infecting geminiviruses are dispersed across boundaries of nation. By doing phylogenetic analysis it is possible to trace the pathway of the long distance movement of virus. Livestock trading has been shown to be significant in PCV2 emergence in many countries [ 62 ].

Analysis of large number of sampling over a long period is required to work out the pathway of these viruses which are emerging as serious threat to human welfare. The ssDNA viruses constitute the widespread, diverse and important group of viruses affecting all three domains of life. Metagenomic mining and characterization of Rep like sequences have led to explosion of CRESS DNA virus data which reveal the ubiquitous presence of these viruses in diverse habitat.

Endogenizations of viral genome and horizontal gene transfer happening across different hosts have revealed the past history of many of the viruses.

Whatever information gathered is only tip of the iceberg. Detection of ssDNA virus like sequences frequently in large number of eukaryotes, suggest that their origin and invasion of hosts might have occurred long time ago and genome fossils embedded in eukaryotic genome only reveal the past lineages of viruses.

Considering its presence in characteristic ecological niches, it may be speculated that ssDNA viruses may have a bigger role in modulation of global ecology and environment.

Publisher's Note. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. National Center for Biotechnology Information , U. Journal List Virusdisease v. Published online Apr Malathi 1 and P. Renuka Devi 2. Renuka Devi. Author information Article notes Copyright and License information Disclaimer. Malathi, Email: moc. Corresponding author. Received Mar 4; Accepted Mar This article has been cited by other articles in PMC.

Abstract Single-stranded ss DNA viruses are extremely widespread, infect diverse hosts from all three domains of life and include important pathogens. Introduction Recent advances in metagenomic sequencing involving large population of viruses in environmental samples have revealed an astonishing volume of virome in every habitat in the biosphere.

Open in a separate window. Classification of ssDNA viruses into families with progress of time. Table 1 Overall properties of ssDNA viruses. Capsid protein The virion particles of the most of the ssDNA viruses have icosahedral morphology, except Inoviridae and Spiraviridae with helical morphology: the pleomorphic 40 nm size enveloped virions are met with only in the case of Pleolipoviridae infecting archaea. Ecology and distribution of ssDNA viruses ssDNA viral genome sequences have been detected in diverse environments, associated with diverse life forms which need to be analyzed to speculate the global impact such distribution will have.

Endogenisation and horizontal gene transfer of ssDNA viruses Deep sequencing of eukaryotic genome increasingly has thrown out abundant and more diverse viral sequences. Horizontal gene transfer Living organism acquire genes not only by vertical transmission but also from other distantly related species through horizontal gene transfer. Evolutionary trends The eukaryotic ssDNA viruses infecting plants and pet animals emerge as threatening pathogens due to high rate of substitution in genome.

Origin and evolution of ssDNA viruses In the context of ever-growing presence of diverse ssDNA viruses, it is interesting to speculate their origin and how different lineages might have separated from each other. Transboundary movement With increasing trade and movement of agricultural commodities it is inevitable that ssDNA viruses move across continents. Concluding remarks The ssDNA viruses constitute the widespread, diverse and important group of viruses affecting all three domains of life.

Footnotes Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Aiewsakun P, Katzourakis A. Endogenous viruses: connecting recent and ancient viral evolution. Mobilisation into cotton and spread of a recombinant cotton leaf curl disease satellite—brief report.

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