Biology 331 Introduction to Virology Class I Viruses Mostly Chapters 9 , 16
© Elsevier, 2011.Principles of Molecular Virology Introduction What is a virus? How are viruses are...
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Transcript of © Elsevier, 2011.Principles of Molecular Virology Introduction What is a virus? How are viruses are...
Principles of Molecular Virology © Elsevier, 2011.
IntroductionIntroduction
• What is a virus?
• How are viruses are different from other organisms?
• Are viruses alive?
• The history of virology how we think about viruses
• Techniques used to study viruses
Principles of Molecular Virology © Elsevier, 2011.
What are viruses?What are viruses?
• Viruses are submicroscopic, obligate intracellular
parasites
• Most too small to be seen by optical microscopes
• Largest virus known (Mimivirus) = 400 nm diameter,
smallest bacteria (Mycoplasma) = 200 nm
• Largest virus genome (Mimivirus, 1.2 Mbp) twice as
big as smallest bacterial genome (Mycoplasma
genitalium, 0.58 Mbp)
Principles of Molecular Virology © Elsevier, 2011.
How viruses are uniqueHow viruses are unique
• Virus particles are produced from the assembly of
preformed components, other biological agents
grow from an increase in the integrated sum of their
components and reproduce by division
• Virus particles (virions) do not grow or divide
• Viruses lack the genetic information that encodes
tools necessary for the generation of metabolic energy
or protein synthesis (ribosomes)
Principles of Molecular Virology © Elsevier, 2011.
Are viruses alive?Are viruses alive?
• Viruses do not reproduce by division but are
assembled from preformed components
• Viruses cannot make their own energy or proteins
• A virus-infected cell is more like a factory than a
womb
Principles of Molecular Virology © Elsevier, 2011.
The history of virologyThe history of virology
• First written record of virus infection ~ 3700 BC
- paralytic poliomyelitis
• Smallpox endemic in China by 1000 BC
• Edward Jenner, 14th May 1796 - smallpox vaccination
• Robert Koch and Louis Pasteur, 1880s
- germ theory of disease
Principles of Molecular Virology © Elsevier, 2011.
The history of virologyThe history of virology
• 1892: Dimitri Iwanowski - "filterable particles”
- smaller than bacteria• 1898: Martinus Beijerinick - tobacco mosaic virus
- "soluble living germ"• 1898: Freidrich Loeffler and Paul Frosch
- foot-and-mouth disease in cattle• 1909: Karl Landsteiner and Erwin Popper
- poliomyelitis in humans• Frederick Twort (1915) and Felix d’Herelle (1917)
- bacteriophages
Principles of Molecular Virology © Elsevier, 2011.
Living host systemsLiving host systems
• 1881: Louis Pasteur - rabies vaccine from rabbits
• 1900: Walter Reed - yellow fever caused by a virus
spread by mosquitoes
• Animal host systems still have their uses in virology:
–To produce viruses that cannot be effectively studied in vitro
(e.g. hepatitis B virus)
–To study the pathogenesis of virus infections (e.g. HIV and SIV)
–To test vaccine safety (e.g. oral poliovirus vaccine)
Principles of Molecular Virology © Elsevier, 2011.
Living host systemsLiving host systems
• 1980's: transgenic animals which which carry the
genes of other organisms
• Transgenics are useful for understanding the
pathogenesis of viruses, prions
Principles of Molecular Virology © Elsevier, 2011.
Cell Culture MethodsCell Culture Methods
1949: John Enders propagates poliovirus in human cells
1950s and 1960s: identification and isolation of many viruses
1952: Renato Dulbecco - plaque assay
Principles of Molecular Virology © Elsevier, 2011.
Serological/Immunological MethodsSerological/Immunological Methods
• 1941: George Hirst - haemagglutination of red blood
cells by influenza virus• Improved detection methods for viruses:
Complement fixation tests
Radioimmunoassays
Immunofluorescence (direct detection of virus antigens in infected cells or tissue)
Enzyme-linked immunosorbent assays (ELISAs)
Radioimmune precipitation
Western blot assays
Principles of Molecular Virology © Elsevier, 2011.
Serological/Immunological MethodsSerological/Immunological Methods
Principles of Molecular Virology © Elsevier, 2011.
Monoclonal antibodiesMonoclonal antibodies
Principles of Molecular Virology © Elsevier, 2011.
Ultrastructural StudiesUltrastructural Studies
Centrifugation of virus particles
Principles of Molecular Virology © Elsevier, 2011.
Ultrastructural StudiesUltrastructural Studies
• Spectroscopy - light-scattering properties
• X-ray diffraction
• Nuclear magnetic resonance (NMR)
Principles of Molecular Virology © Elsevier, 2011.
Ultrastructural StudiesUltrastructural Studies
Principles of Molecular Virology © Elsevier, 2011.
Electron MicroscopyElectron Microscopy
Principles of Molecular Virology © Elsevier, 2011.
Molecular BiologyMolecular Biology
Experimental techniques used to study the structure and function of biomolecules and their interactions
Focus on the virus genome:
• Molecular cloning
• Nucleotide sequencing
• Microarrays
Principles of Molecular Virology © Elsevier, 2011.
Nucleic acid hybridizationNucleic acid hybridization
Blotting and probing for detection of DNA (Southern blot), RNA (Northern blot), proteins (Western blot)
Principles of Molecular Virology © Elsevier, 2011.
Polymerase chain reaction (PCR)Polymerase chain reaction (PCR)
Principles of Molecular Virology © Elsevier, 2011.
BioinformaticsBioinformatics
Principles of Molecular Virology © Elsevier, 2011.
Further ReadingFurther Reading
Alberts, B., Bray, D., Hopkin,K., Johnson, A., Lewis, J., Raff, M., Roberts, K., Walter, P. and Johnson, A. (2009). Essential Cell Biology. 3rd Edition. Garland Science, New York. ISBN 0815341296
Forterre, P. (2010) Defining life: the virus viewpoint. Orig Life Evol Biosph. 40(2): 151-160
Hendrix, R.W. (2003). Bacteriophage genomics. Current Opinion in Microbiology, 6: 506–511
Lesk, A. Introduction to Bioinformatics. (2008) OUP Oxford; 3rd edition
Moreira, D., and López-García, P. (2009). Ten reasons to exclude viruses from the tree of life Nature Reviews Microbiology, 7 (4): 306-311
Primrose, S. and Twyman, R. Principles of Gene Manipulation and Genomics. (2006) Wiley-Blackwell 7th Edition
Raoult D, Forterre P. (2008) Redefining viruses: lessons from Mimivirus. Nat Rev Microbiol. 6 (4): 315-319
Sompayrac, L. How the Immune System Works. (2008) Wiley-Blackwell. 3rd edition
Villarreal L. (2004) Are viruses alive? Scientific American 291 (6): 100-105