Viral Genome

8 Key excerpts on "Viral Genome"

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  eBook - ePub

  Basic Virology

  • Martinez J. Hewlett, David Camerini, David C. Bloom(Authors)
  • 2021(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  In essence, viruses are collections of genetic information directed toward one end: their own replication. They are the ultimate and prototypical example of “selfish genes.” The Viral Genome contains the “blueprints” for virus replication enciphered in the genetic code, and must be decoded by the molecular machinery of the cell that it infects to gain this end. Viruses are thus obligate intracellular parasites dependent on the metabolic and genetic functions of living cells.

  Given the essential simplicity of virus organization – a genome containing genes dedicated to self‐replication surrounded by a protective protein shell – it has been argued that viruses are nonliving collections of biochemicals whose functions are derivative and separable from the cell. Yet this generalization does not stand up to the increasingly detailed information accumulating describing the nature of viral genes, the role of viral infections in evolutionary change, and the evolution of cellular function. A view of viruses as constituting a major subdivision of the biosphere, as ancient as and fully interactive and integrated with the three great branches of cellular life, becomes more strongly established with each investigational advance.

  It is a major problem in the study of biology at a detailed molecular and functional level that almost no generalization is sacred, and the concept of viruses as simple parasitic collections of genes functioning to replicate themselves at the expense of the cell they attack does not hold up. Many generalizations will be made in the survey of the world of viruses introduced in this book; most if not all will be ultimately classified as being useful, but unreliable, tools for the full understanding and organization of information.

  Even the size range of Viral Genomes, generalized to range from one or two genes to a few hundred at most (significantly less than those contained in the simplest free‐living cells), cannot be supported by a close analysis of data. While it is true that the vast majority of viruses studied range in size from smaller than the smallest organelle to just smaller than the simplest cells capable of energy metabolism and protein synthesis, the mycoplasma and simple unicellular algae, the recently discovered mimivirus (distantly related to poxviruses such as smallpox or variola) contains nearly 1000 genes and is significantly larger than the smallest cells. With such caveats in mind, it is still appropriate to note that despite their limited size, viruses have evolved and appropriated a means of propagation and replication that ensures their survival in free‐living organisms that are generally between 10 and 10 000 000 times their size and genetic complexity.

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  Basic Virology

  • Edward K. Wagner, Martinez J. Hewlett, David C. Bloom, David Camerini(Authors)
  • 2009(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  In essence, viruses are collections of genetic information directed toward one end: their own replication. They are the ultimate and prototypical example of “selfish genes.” The Viral Genome contains the “blueprints” for virus replication enciphered in the genetic code, and must be decoded by the molecular machinery of the cell that it infects to gain this end. Viruses are; thus, obligate intracellular parasites dependent on the metabolic and genetic functions of living cells. Given the essential simplicity of virus organization – a genome containing genes dedicated to self replication surrounded by a protective protein shell – it has been argued that viruses are nonliving collections of biochemicals whose functions are derivative and separable from the cell. Yet this generalization does not stand up to the increasingly detailed information accumulating describing the nature of viral genes, the role of viral infections on evolutionary change, and the evolution of cellular function. A view of viruses as constituting a major C H A P T E R 1 4 BASIC VIROLOGY PART I VIROLOGY AND VIRAL DISEASE subdivision of the biosphere as ancient as and fully interactive and integrated with the three great branches of cellular life becomes more strongly established with each investigational advance. It is a major problem in the study of biology at a detailed molecular and functional level that almost no generalization is sacred, and the concept of viruses as simple parasitic collections of genes functioning to replicate themselves at the expense of the cell they attack does not hold up. Many generalizations will be made in the survey of the world of viruses introduced in this book, most if not all will be ultimately classified as being useful, but unreliable tools for the full understanding and organization of information.

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  Harnessing the Power of Viruses

  • Boriana Marintcheva(Author)
  • 2017(Publication Date)
  • Academic Press

    (Publisher)

  The flu virus genome, for example, contains only 15,000 nucleotides. For comparison the human genome is 3,200,000,000 nucleotides or approximately 200,000 times longer. Needless to say, viruses have to be superefficient, in their quest to invade the host cell and to propagate. Bacteriophage Qβ is among the smallest RNA viruses with a genome built from 4217 nucleotides and only 4 genes. Among the smallest known animal DNA viruses is TT virus whose genome is comprised of less than 4000 nucleotides and 4 predicted genes. On the opposite side of the scale is the giant Megavirus chilensis with genome as large as 1.3 MB coding for 1000 genes. What functions Viral Genomes code for is a tantalizing question. Analysis of Viral Genome sequences revealed that approximately 80% of the Viral Genomes code for virus-specific genes, many of which have no known homologues or known function. Figure 1.6 Diversity of Viral Genomes. 1.2.3. Envelopes Viral envelopes are built from phospholipid bilayers that resemble cellular membrane. The lipid components are purely of host origin, whereas the protein components are virally coded. Most of the envelope proteins are integral glycoproteins with critical function for virus–host interactions. Similar to the proteins on the outside surface of naked viruses, they function as ligands to host receptors. Enveloped viruses acquire their envelopes as they are leaving the host cell. 1.2.4. Additional Virion Components Some enveloped viruses have distinctive protein layer spanning the space between the capsid and the envelope. In herpesviruses, this layer is named tegument, whereas in HIV and influenza a matrix (Fig. 1.5). It is thought that the extra layer is stabilizing the virion filling the gap of nonexisting direct connections between the nucleocapsid and the envelope. A small number of extra molecules are found in the virions (viral particles) of many viruses

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  Virology

  • Maria Carla Saleh, Felix Augusto Rey(Authors)
  • 2021(Publication Date)
  • Wiley-ISTE

    (Publisher)

  et al. 2012). These features are shared by the 100 known herpesviruses that infect invertebrates or vertebrates, eight infecting humans and two, EBV and KSHV, are considered group 1 carcinogens by the WHO. Worldwide EBV prevalence is high, greater than 90%, with the majority of infections being asymptomatic.

  1.3. Genomes

  Viral Genomes encode the genes necessary for viral replication, expression, the assembly of new virions, proteins that regulate the timing of viral processes, as well as proteins that modulate host cells and promote the spread to new cells, and evasion of host cell surveillance. In addition to being single- or double-stranded, DNA virus genomes can be linear or circular, or may have more complex configurations, similar to the gapped DNA genomes of the hepadnaviruses (like HBV). Of the known viruses with linear ssDNA genomes, most are small, with lengths ranging from 4 to 12.5 kilobases, encoding less than five gene products. Those with circular ssDNA genomes range from 1.8 to 24.9 kilobases and encode less than five gene products. Those with circular dsDNA genomes can be from 4.5 to 610 kilobases in size (Hulo et al. 2011). Those with linear dsDNA Viral Genomes fall between 14.5 and 2,500 kilobases in size. Overall, linear dsDNA genomes are usually longer than ssDNA genomes and as such, encode a greater number of genes.

  Viral particles that carry smaller Viral Genomes tend to encode fewer genes and rely heavily on the host cell machinery for the expression and replication of their genomes. DNA viruses with large genomes are often less reliant on the host cell for replication. But all Viral Genomes, large or small, must produce mRNA that can be translated by host ribosomes.

  Figure 1.2.

  DNA Viral Genomes can be linear, circular, single- and double-stranded. In virus particles, the small double-stranded HPV genome is decorated with host histones. Certain HPV strains are known to integrate into the host genome, converting from a circular to linear integrated state. The KSHV genome in virus particles is linear; during latency, the KSHV genome becomes circularized and decorated with viral proteins and cellular histone proteins to form the KSHV episome. Created with BioRender

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  Clinical Virology Manual

  • Richard L. Hodinka, Stephen A. Young, Benjamin A. Pinksy, Richard L. Hodinka, Stephen A. Young, Benjamin A. Pinksy(Authors)
  • 2016(Publication Date)
  • ASM Press

    (Publisher)

  Another key choice is whether to include partial or full genome sequences. For obvious reasons, including earlier technologic issues with sequencing long regions of nucleic acid and the management of sequencing information, earlier classification approaches were often based on partial genome sequences of viruses. For example, the RNA-dependent RNA-polymerase (RdRp) protein sequence was used as one tool to understand relatedness of families within the order Picornavirales and could be used to distinguish members of different genera within the family Reoviridae (27). Subgenomic analysis of one or multiple genes will not reveal the nature of all genetic changes within a virus and may not confidently classify a virus that is being studied within an appropriate taxonomic framework. The increased use of whole genome sequencing rather than sequencing only subgenomic regions has led to instances in which greater diversity or variants are identified from previously studied viral populations (49). Whole genome approaches have also uncovered previously undescribed evolutionary relationships, including evidence of interspecies transmission and related recombination events (50), that can then assist in how viruses are classified. When these approaches are applied, they can be used to generate more consistent nomenclature (39). This new information identified by analysis of a complete genome is important because it increases our awareness of relatedness between individual viruses being studied and improves our knowledge of viral epidemiology and pathophysiology. The impact of the viral metagenome on understanding the virome and characterizing virus components within primary specimens or natural samples should also be noted. High-throughput deep-sequencing approaches have played important roles in the discovery of viruses and viral communities, or the virome, within primary specimens and biological samples (51)

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  Handbook of Molecular Microbial Ecology II

  Metagenomics in Different Habitats

  • Frans J. de Bruijn(Author)
  • 2011(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  31 on planet Earth) biological entities that likely infect and disrupt all cellular organisms (see Chapters 2, 4, and 5 in this volume). Viral metagenomics, the characterization and evaluation of viral consortia from environmental samples, has shown that viruses are unexpectedly diverse. More than 5000 viral genotypes or “species” have been detected in 100 L of seawater, and ∼1 million species have been found in 1 k of sediment [Breitbart et al., 2002, 2004; Angly et al., 2006]. Viromes collected from across the world have also shown that viral species are globally distributed (everything is everywhere) but that the relative abundance of each species is restricted by local selection (for review see Srinivasiah et al. [2008] and Vega Thurber (2009)). Lastly, viromics has shown that viral functional diversity, as well as its influence on host adaptation, has been vastly underestimated (for review see Rohwer and Vega Thurber (2009)).

  Some physical characteristics (e.g., capsid durability) make viruses amenable to purification. However, other aspects of their biology significantly limit viral observation, maintenance, and manipulation, including: (1) the wide range of viral particle sizes, shapes, densities, and sensitivities; (2) viral decay; and (3) variation in Viral Genome type (DNA vs. RNA and single- vs. double-stranded) and length. For example, some archaeal and eukaryotic viruses (e.g., fuselloviruses, asfraviruses, and iridoviruses) can withstand temperatures above 55°C for extended periods of time [Fauquet et al., 2005]; but depending on the prevailing abiotic and biotic conditions, some marine viral particles decay on the order of hours (∼2.5–12 h) to days [Suttle and Feng, 1992].

  Additionally, the majority of viruses cannot be grown in pure culture because their hosts are recalcitrant to cultivation. The lack of a single phylogenetic marker amongst viral families requires that alternative approaches to gene marker-based phylogenetics (e.g., the 16S rRNA gene sequence commonly used for Bacteria and Archaea; see Chapter 15, Vol. I) be used for the evaluation of viral consortia in environmental samples [Rohwer and Edwards, 2002]. Finally, the disparate phenetic parameters (e.g., genome type, host range, and morphological and physical characteristics, as well as genetic and genomic sequence similarities) used in viral taxonomy have generated polyphyletic viral families and obscured the evolutionary relationships between taxa and sequences [Lawrence et al., 2002]. Therefore, any researcher interested in generating and analyzing viromes must confront a suite of both methodological and analytical challenges.

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  Viruses

  Biology, Applications, and Control

  • David Harper(Author)
  • 2011(Publication Date)
  • Garland Science

    (Publisher)

  Viruses with inserts are maintained using another source to supply the missing functions. This can be a complete, co-infecting ‘helper’ virus, a modified helper virus that can supply the missing functions but not replicate itself (a suicide virus), or viral genes stably expressed in the cell used to culture the virus. Since virus replication often damages or kills infected cells, many approaches use defective viruses, which in some systems contain little viral nucleic acid other than packaging signals. Use of viral vectors for vaccine production is an important aspect of this work, and is covered in more detail in Chapter 5, where the effect of folding and structure on protein immunogenicity is also reviewed. 9.2 SEQUENCING Matching the development of an understanding of the nature of and the ability to manipulate the genetic material is the need to understand what it says and what it means. CHAPTER 9 Viruses, Vectors, and Genomics 227 Huge amounts of sequence data are now available, and more is becoming available at an ever-increasing rate ( Figure 9.3 ). However, it is important to remember that while a genome sequence can usually be used to predict the order and type of amino acids in the polypeptides that can be produced from it, the nature of any final protein product is by no means a simple or even predictable extension from the genetic sequence. There are a large number of intermediate steps (see Table 9.2). During the early part of the 1970s, a number of highly labor-intensive tech-niques were developed for identifying the order of bases in a molecule of DNA or RNA. Using such techniques, Fiers and co-workers reported the sequence of the 3659 bases of the RNA making up the genome of the MS2 bacteriophage in 1976. This was the first whole genome sequence to be characterized.

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  Viruses

  Biology, Applications, and Control

  • David Harper(Author)
  • 2011(Publication Date)
  • Garland Science

    (Publisher)

  Even the small absolute size of many Viral Genomes is no longer always helpful and they are actually too small for many of the sequencing systems now in development. It is an unavoidable consequence of the relatively small size of virus genomes that they benefit far less from the development of the latest ultra-high-throughput systems. The often-cited lower cost of these systems may not apply for short Viral Genomes, since the actual cost per run can be high, and if the full capacity of the system is not used the cost per base can rise very significantly. It is possible to counter this by loading multiple samples in a single well, but this can cause problems if viruses are closely related, with the possibility of a single consensus sequence being generated for multiple viruses. Tagging of individual sequences may now be used to permit this. However, older systems may still be used to analyze Viral Genomes and other short nucleic acids.

  As of 2009, the GenBank DNA sequence database (Figure 9.3 ) contained approximately 2000 complete Viral Genome sequences (including at least one representative of every virus family known to infect humans), and many more partial sequences. However, given that the estimated number of viruses on the planet is greater than 10,000,000,000,000,000,000,000,000, 000,000 (1031 ) it is clear that we have a long way to go before we can claim to have characterized a significant percentage of viruses.

  As more and more sequences become available, understanding of virus function at this most basic level is increasing, with viruses previously considered to be closely related being identified as significantly different (as with hepatitis E virus, which has been moved from the Caliciviridae to its own family, the Hepeviridae) and with relationships becoming apparent that would not otherwise be detected (for example, similarities between the Herpesviridae and the tailed DNA bacteriophages).

  As with many systems studied, work with (relatively) simpler viral systems is likely to underpin understanding of more complex systems.

  Junk or not junk?

  As noted, viruses have very dense coding within their genomes (sometimes exceeding 100% of the genome by the use of overlapping genes), but the human genome does not. Less than 2% of the human genome codes for proteins, prompting some observers to call the rest “junk DNA.”

  As is often the case, this simple and dismissive term reflects a limited understanding of a complex situation. DNA specifying many controlling factors as well as a range of non-protein effector molecules lies in these “junk” regions. These latter include the functional RNAs of the cell (transfer and ribosomal RNAs) as well as a range of small RNAs such as those of the RNAi system. Some of the DNA is likely to represent genuine “junk,” such as defunct retroviral elements (though even these may have a role, for example in moderating tolerance of fetal tissue during pregnancy), but much of it will not.

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