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Virus Genomes

Virus Genomes. How does the diversity of virus genomes affect virus replication? Representative virus genomes illustrate the genetic mechanisms that affect viruses. Structure and Complexity of Virus Genomes. Virus genomes may be: either DNA or RNA

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Virus Genomes

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  1. Virus Genomes How does the diversity of virus genomes affect virus replication? Representative virus genomes illustrate the genetic mechanisms that affect viruses. Principles of Molecular Virology

  2. Structure and Complexity of Virus Genomes Virus genomes may be: either DNA or RNA single stranded or double stranded linear, circular, or segmented structure Virus genomes range in size from approximately 2,500 (nt) (Geminivirus) to approximately 1.2 million bp (Mimivirus) - twice as big as the smallest bacterial genome (Mycoplasma genitalum) Principles of Molecular Virology

  3. Structure and Complexity of Virus Genomes Virus genomes must contain information encoded in a way that can be recognized and decoded by the host cell Virus genomes have been intensively studied through molecular biology Principles of Molecular Virology

  4. Molecular Genetics Important questions: Composition - DNA or RNA, single-stranded or double-stranded, linear or circular Size and number of segments Nucleotide sequence Terminal structures Coding capacity - open reading frames Regulatory signals - transcription enhancers, promoters, and terminators Principles of Molecular Virology

  5. Virus Genetics Biochemical analysis Focal immunoassays Physical analysis Transformed foci Recombination maps Reassortment groups  Physical maps Restriction maps Transcription maps Translation maps Principles of Molecular Virology

  6. Virus Mutants Strain - different lines or isolates of the same virus Type - different serotypes of the same virus Variant - a virus whose phenotype differs from the original wild-type strain but the genetic basis is not known Spontaneous Mutations Induced Mutations Principles of Molecular Virology

  7. Genetic Interactions between Viruses- Complementation Principles of Molecular Virology

  8. Genetic Interactions between Viruses- Recombination Intramolecular recombination via strand breakage and re-ligation Intramolecular recombination by "copy-choice" Reassortment in viruses with segmented genomes Principles of Molecular Virology

  9. Nongenetic Interactions Between Viruses Heterozygosis Interference Phenotypic mixing  Principles of Molecular Virology

  10. Small DNA Genomes - Parvoviruses Parvovirus genome - linear, non-segmented, single-stranded DNA of about 5 kb Principles of Molecular Virology

  11. Small DNA Genomes - Polyomaviruses Polyomavirus genome - double-stranded, circular DNA molecules of approximately 5 kbp Principles of Molecular Virology

  12. Large DNA Genomes - Adenoviruses Adenovirus genome - linear, double-stranded DNA of 30-38 kbp, containing 30 to 40 genes Principles of Molecular Virology

  13. Large DNA Genomes - Herpesviruses Herpesvirus genome: up to 235 kbp, linear, double-stranded DNA Principles of Molecular Virology

  14. Large DNA Genomes - Poxviruses Poxvirus genome - linear, double-stranded DNA from 140 – 290 kbp Principles of Molecular Virology

  15. Positive-Strand RNA Viruses Principles of Molecular Virology

  16. Negative-Strand RNA Viruses Principles of Molecular Virology

  17. Segmented and Multipartite Virus Genomes Segmented virus genomes are divided into two or more physically separate molecules of nucleic acid, all of which are packaged into a single virus particle Multipartite virus genomes are also segmented, but each genome segment is packaged into a separate virus particle Principles of Molecular Virology

  18. Reverse Transcription and Transposition Simple transposons do not undergo reverse transcription, found in prokaryotes (e.g. bacteriophage Mu): Principles of Molecular Virology

  19. Reverse Transcription and Transposition Retrotransposons resemble retrovirus genomes, move by means of a transcription/reverse transcription/ integration mechanism and are found in eukaryotes (Metaviridae and Pseudoviridae): Principles of Molecular Virology

  20. Retrovirus genomes have 4 unique features: They are the only viruses that are truly diploid They are the only RNA viruses whose genome is produced by cellular transcriptional machinery (without a virus-encoded polymerase) They are the only viruses whose genome requires a specific cellular RNA (tRNA) for replication They are the only positive-sense RNA viruses whose genome does not serve directly as mRNA immediately after infection Principles of Molecular Virology

  21. Reverse Transcription Principles of Molecular Virology

  22. Retrovirus long terminal repeats (LTRs) Principles of Molecular Virology

  23. Retrovirus Integration Principles of Molecular Virology

  24. "Reversiviruses" Hepatitis B virus: Cauliflower mosaic virus: Principles of Molecular Virology

  25. Evolution and Epidemiology Three theories to explain the origin of viruses: Regressive evolution Cellular origins Independent entities Principles of Molecular Virology

  26. Summary Molecular biology has put emphasis on the structure and function of the virus genome Sequences and structures at the ends of virus genomes are important Common patterns of genetic organization seen in virus superfamilies suggest either that many viruses have evolved from common ancestors Principles of Molecular Virology

  27. Further Reading Barr, J.N., and Fearns, R. (2010). How RNA viruses maintain their genome integrity. J Gen Virol. 91(6): 1373-1387 Beck, J. and Nassal M. (2007). Hepatitis B virus replication. World J Gastroenterol. 13 (1): 48-64 Bieniasz, P.D. (2009) The Cell Biology of HIV-1 Virion Genesis. Cell Host & Microbe 5(6): 550-558 Craig, N.L. et al. (2002). Mobile DNA. ASM Press, Washington, D.C. ISBN 1555812090 Domingo, E., Webster, R.G., and Holland, J.J. (2000). Origin and Evolution of Viruses. Academic Press, San Diego, CA. ISBN 0122203607 Forterre, P. and Prangishvili, D. (2009). The Great Billion-year War between Ribosome- and Capsid-encoding Organisms (Cells and Viruses) as the Major Source of Evolutionary Novelties. Annals of the New York Academy of Sciences. 1178: 65–77 Hutchinson, E.C., von Kirchbach, J.C., Gog, J.R. and Digard, P. (2010) Genome packaging in influenza A virus. J Gen Virol 91: 313-328 Mertens, P. (2004). The dsRNA viruses. Virus Research, 101: 3–13 Miller, E.S. et al. (2003). Bacteriophage T4 genome. Microbiology and Molecular Biology Review, 67: 86–156. Moya, A. et al. (2004). The population genetics and evolutionary epidemiology of RNA viruses. Nature Reviews: Microbiology, 2: 279–288 Nguyen, M. and Haenni, A.L.(2003). Expression strategies of ambisense viruses. Virus Research 93: 141-150 Raoult D,. et al. (2004). The 1.2-megabase genome sequence of Mimivirus. Science, 306: 1344-1350 Rice, G. et al. (2004). The structure of a thermophilic archaeal virus shows a double-stranded DNA viral capsid type that spans all domains of life. Proceedings of the National Academy of Science USA, 101: 7716–7720 Steinhauer, D.A. and Skehel, J.J. (2002). Genetics of influenza viruses. Annual Review of Genetics, 36: 305–332. Van Etten, J.L., Lane, L.C. and Dunigan, D.D. (2010). DNA Viruses: The Really Big Ones (Giruses). Annual Review of Microbiology 64: 83–99 Wagner, M. et al. (2002). Herpesvirus genetics has come of age. Trends in Microbiology, 10: 318–324 Principles of Molecular Virology

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