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Principles of Molecular Virology © Elsevier, 2011.
Virus GenomesVirus 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 © Elsevier, 2011.
Structure and Complexity of Virus GenomesStructure 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 © Elsevier, 2011.
Structure and Complexity of Virus GenomesStructure 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 © Elsevier, 2011.
Molecular GeneticsMolecular 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 © Elsevier, 2011.
Virus GeneticsVirus 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 © Elsevier, 2011.
Virus MutantsVirus 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 © Elsevier, 2011.
Genetic Interactions between VirusesGenetic Interactions between Viruses- Complementation- Complementation
Principles of Molecular Virology © Elsevier, 2011.
Genetic Interactions between VirusesGenetic Interactions between Viruses- Recombination- Recombination
• Intramolecular recombination via strand breakage and
re-ligation
• Intramolecular recombination by "copy-choice"
• Reassortment in viruses with segmented genomes
Principles of Molecular Virology © Elsevier, 2011.
Nongenetic Interactions Between VirusesNongenetic Interactions Between Viruses
• Heterozygosis
• Interference
• Phenotypic mixing
Principles of Molecular Virology © Elsevier, 2011.
Small DNA Genomes - Small DNA Genomes - ParvovirusesParvoviruses
Parvovirus genome - linear, non-segmented, single-stranded DNA of about 5 kb
Principles of Molecular Virology © Elsevier, 2011.
Small DNA Genomes - Small DNA Genomes - PolyomavirusesPolyomaviruses
Polyomavirus genome - double-stranded, circular DNA molecules of approximately 5 kbp
Principles of Molecular Virology © Elsevier, 2011.
Large DNA Genomes - Large DNA Genomes - AdenovirusesAdenoviruses
Adenovirus genome - linear, double-stranded DNA of 30-38 kbp, containing 30 to 40 genes
Principles of Molecular Virology © Elsevier, 2011.
Large DNA Genomes - Large DNA Genomes - HerpesvirusesHerpesviruses
Herpesvirus genome:
up to 235 kbp,
linear,
double-stranded
DNA
Principles of Molecular Virology © Elsevier, 2011.
Large DNA Genomes Large DNA Genomes - Poxviruses- Poxviruses
Poxvirus genome - linear, double-stranded DNA from 140 – 290 kbp
Principles of Molecular Virology © Elsevier, 2011.
Positive-Strand RNA VirusesPositive-Strand RNA Viruses
Principles of Molecular Virology © Elsevier, 2011.
Negative-Strand RNA VirusesNegative-Strand RNA Viruses
Principles of Molecular Virology © Elsevier, 2011.
Segmented and Segmented and Multipartite Virus GenomesMultipartite 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 © Elsevier, 2011.
Reverse Transcription and TranspositionReverse Transcription and Transposition
Simple transposons do not undergo reverse transcription, found in prokaryotes (e.g. bacteriophage Mu):
Principles of Molecular Virology © Elsevier, 2011.
Reverse Transcription and TranspositionReverse 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 © Elsevier, 2011.
Retrovirus genomes have 4 unique features: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 © Elsevier, 2011.
Retrovirus long terminal repeats (LTRs)Retrovirus long terminal repeats (LTRs)
Principles of Molecular Virology © Elsevier, 2011.
"Reversiviruses""Reversiviruses"
Hepatitis B virus: Cauliflower mosaic virus:
Principles of Molecular Virology © Elsevier, 2011.
Evolution and EpidemiologyEvolution and Epidemiology
Three theories to explain the origin of viruses:
• Regressive evolution
• Cellular origins
• Independent entities
Principles of Molecular Virology © Elsevier, 2011.
SummarySummary
• 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 © Elsevier, 2011.
Further ReadingFurther 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