Virology week6

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  • Virology week6

    1. 1. Virology - Introduction03/04/12 MASDIANA PADAGA 1
    2. 2. Why are viruses important ?• Viruses cause disease in animals of economicand/or welfare importance • Diagnose viral disease (clinical/lab tests) • Advise clients control (risk to other animals)• Animal viruses may pose risk to human health(zoonosis)• Can act as important models for human disease•VIRUSES CAN BE USEFUL VACCINE DEVELOPMENT GENE THERAPY TOOLS TO INVESTIGATE HOST CELLS
    3. 3. What are Viruses?• A virus is a non- cellular particle made up of genetic material and protein that can invade living cells. 03/04/12 MASDIANA PADAGA 3
    4. 4. Size of Viruses03/04/12 MASDIANA PADAGA 4
    5. 5. Virus Classification • International Committee on Taxonomy of Viruses chemical characteristics, genome type, replication strategy, diseases, vectors, geographical distribution, host species nucleotide sequenceorder family subfamily genus species/strain/type-virales -viridae -virinae -virus -virusmononegavirales paramyxoviridae paramyxovirinae morbillivirus canine distemper virus herpesviridae alphaherpesvirinae varicellovirus equid herpesvirus 1 03/04/12 MASDIANA PADAGA 5
    6. 6. Basic virus structureDNA Capsid Naked or + Nucleocapsid = protein capsid virusRNA Lipid membrane, Nucleocapsid + Enveloped virus glycoproteins03/04/12 MASDIANA PADAGA 6
    7. 7. Virion (virus particle) structure 1. genome nucleocapsid 2. capsid ± 3. envelopeenvelope glycoproteins 03/04/12 MASDIANA PADAGA 7
    8. 8. DNA Viruses03/04/12 MASDIANA PADAGA 8
    9. 9. RNA Viruses03/04/12 MASDIANA PADAGA 9
    10. 10. 1- Viral Nucleic Acids DNA or RNA [cell genetic material is DNA] ss or ds ss -/+/mixed sense [mRNA= +sense] linear or circular segmented/non-segmented size 2-300 kb(p) [cell genome 3x106kbp] Genetic ‘heritage’ Codes for virus proteins Controls virus protein production - promoters, transcriptional enhancers, splice signals Contains elements necessary for replication and genome packaging
    11. 11. Viral ProteinsStructural Components of capsid (protective coat) and other components of the virionNon-structural Required for viral replication and interaction with host
    12. 12. 2- Nucleocapsid Capsid is protein coat that protects the nucleic acid: physical, chemical, enzymatic attack Nucleocapsid comprises the capsid and enclosed nucleic acid facilitates entry into cell and delivery of nucleic acid exposed to immune system genome nucleocapsid capsid
    13. 13. Viruses come in a variety of shapes and sizes dictated by their protein and nucleic acid composition - but there are common elements in their architecture due to SYMMETRY ICOSAHEDRAL HELICAL03/04/12 MASDIANA PADAGA 13
    14. 14. Capsid symmetry Icosahedral Helical Naked capsid Enveloped Matrix Lipid Glycoprotein03/04/12 MASDIANA PADAGA 14
    15. 15. Icosahedral (or cubic)20 faces each face an equilateral triangleaxes of 2-, 3- and 5-fold rotational symmetry Some icosahedralCapsomer structure enclosing maximum volume animal viruses are enveloped Foot and mouth disease virus (picornavirus) herpesvirus adenovirus
    16. 16. http://www.ncbi.nlm.nih.gov/ICTVdb/Images/Ackerman/Animalvi/Adenovir/799- 16.htm03/04/12 Electron Adenovirus micrographMASDIANA PADAGA Icosahedral naked capsid viruses Crystallographic model16 Foot and mouth disease virus http://virology.wisc.edu/virusworld/ICTV8/fmd-foot-and-mouth- ictv8.jpg
    17. 17. Icosahedral enveloped viruseshttp://web.uct.ac.za/depts/mmi/stannard/emimages.html http://virology.wisc.edu/virusworld/images/herpescapsid. GIF Herpes simplex virus Herpes simplex virus Electron micrograph Nucleocapsid cryoEM model 03/04/12 MASDIANA PADAGA 17
    18. 18. HelicalSimple viruses with smallgenomes use this architecture toprovide protection for thegenome without the need toencode multiple capsid proteins. Rabies virus (rhabdovirus)
    19. 19. HelicalAll animal viruseswith helicalsymmetry areENVELOPED 03/04/12 MASDIANA PADAGA 19 paramyxovirus
    20. 20. Helical enveloped viruseshttp://web.uct.ac.za/depts/mmi/stannard/fluvirus. http://web.uct.ac.za/depts/mmi/stannard/paramyx.html html Influneza A virus Paramyxovirus Electron Electron 03/04/12 micrograph MASDIANA PADAGA micrograph 20
    21. 21. 3 – Virus Envelope Envelopes are LIPID BILAYERS acquired from cellular membranes e.g. endoplasmic reticulum, nuclear membrane, plasma membrane  viral proteins are associated with/inserted into membrane – surface proteins often glycosylated Adsorption and entry of virus into cells (and exit) -access to target cells -binding to receptors -fusion of envelope with cellular membranes to release genome Interaction with immune system components - binding of antibody - Targets of immune system
    22. 22. Complex Virus Structures Most animal viruses fall into three structural classes, helical capsid (enveloped) icosahedral capsid (nonenveloped) or icosahedral capsid (enveloped)However, more complex structures do exist e.g. pox viruses
    23. 23. 5 BASIC TYPES OF VIRAL STRUCTURE icosahedral nucleocapsid nucleocapsid lipid bilayer ICOSAHEDRAL ENVELOPED ICOSAHEDRAL helical nucleocapsid COMPLEX nucleocapsid lipid bilayer glycoprotein spikes = peplomers HELICAL ENVELOPED HELICAL 03/04/12 MASDIANA PADAGA 23Adapted from Schaechter et al., Mechanisms of Microbial Disease
    24. 24. Stability of Viruses•Non enveloped viruses more ‘hardy’ than enveloped viruses (e.g. foot and mouth disease hardier than influenza virus)•Different viruses have differential ability to survive• sensitive to temperature, pH, dessication, lipid solvents,detergents Most inactivated at >55-60oC Detergents used to disrupt viral envelopes Rotavirus survives pH of stomach•Clinical sample collection / Diagnostics
    25. 25. Properties of enveloped viruses• Envelope is sensitive • Consequences to – Must stay wet during – Drying transmission – Heat – Transmission in large droplets and secretions – Detergents – Cannot survive in the – Acid gastrointestinal tract – Do not need to kill cells in order to spread – May require both a humoral and a cellular immune response Adapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical Microbiology, 5th edition, Elsevier Mosby, Philadelphia, 03/04/12 MASDIANA PADAGA 25
    26. 26. Properties of naked capsid viruses • Capsid is resistant to • Consequences – Drying – Can survive in the – Heat gastrointestinal tract – Detergents – Retain infectivity on drying – Acids – Survive well on – Proteases environmental surfaces – Spread easily via fomites – Must kill host cells for release of mature virus particles – Humoral antibody response may be sufficient to neutralize infectionAdapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical PADAGA 5th edition, Elsevier Mosby, Philadelphia, PA , 26 6-4 03/04/12 MASDIANA Microbiology, Box
    27. 27. BASIC STEPS IN VIRAL LIFE CYCLE• ADSORPTION• PENETRATION (injection) of viral DNA or RNA• UNCOATING AND ECLIPSE• SYNTHESIS OF VIRAL NUCLEIC ACID AND PROTEIN (REPLICATION)• ASSEMBLY (maturation) of the new viruses• RELEASE of the new viruses into the environment (cell lyses) 03/04/12 MASDIANA PADAGA 27
    28. 28. ADSORPTION• TEMPERATURE INDEPENDENT• REQUIRES VIRAL ATTACHMENT PROTEIN• CELLULAR RECEPTORS03/04/12 MASDIANA PADAGA 28
    29. 29. PENETRATION enveloped virus •FUSION WITH PLASMA MEMBRANE •ENTRY VIA ENDOSOMES03/04/12 MASDIANA PADAGA 29
    30. 30. 03/04/12 MASDIANA PADAGA 30
    31. 31. PENETRATION - ENVELOPED VIRUSES 03/04/12 MASDIANAfrom Schaechter et al, Mechanisms of Microbial Disease, 3rd ed, 1998 PADAGA 31
    32. 32. PENETRATION NON-ENVELOPED VIRUSESentry directlyacross plasmamembrane: 03/04/12 MASDIANA PADAGA 32
    33. 33. 03/04/12 MASDIANA PADAGA 33
    34. 34. UNCOATING• NEED TO MAKE GENOME AVAILABLE• ONCE UNCOATING OCCURS, ENTER ECLIPSE PHASE• ECLIPSE PHASE LASTS UNTIL FIRST NEW VIRUS PARTICLE FORMED03/04/12 MASDIANA PADAGA 34
    35. 35. SYNTHESIS OF VIRAL NUCLEIC ACID AND PROTEIN• MANY STRATEGIES• NUCLEIC ACID MAY BE MADE IN NUCLEUS OR CYTOPLASM• PROTEIN SYNTHESIS IS ALWAYS IN THE CYTOPLASM03/04/12 MASDIANA PADAGA 35
    36. 36. ASSEMBLY AND MATURATION• NUCLEUS RELEASE• CYTOPLASM • LYSIS• AT MEMBRANE • BUDDING THROUGH PLASMA MEMBRANE • NOT EVERY RELEASED VIRION IS INFECTIOUS03/04/12 MASDIANA PADAGA 36
    37. 37. epithelial cells - adenovirus uninfected 03/04/12 early infection MASDIANA PADAGA late infection 37slides from CDC
    38. 38. Bacteriophages• Bacteriophages ( phages ) are obligate intracellular parasites that multiply inside bacteria by making use of some or all of the host biosynthetic machinery . They are viruses that infect bacteria.03/04/12 MASDIANA PADAGA 38
    39. 39. Composition of Bacteriophage• Nucleic acid: either DNA or RNA but not both – ds DNA, ss RNA, ss DNA – unusual or modified bases – encode 3-5 gene products to over 100 gene products• Protein: function in infection and protect the nucleic acid 03/04/12 MASDIANA PADAGA 39
    40. 40. Structure of Bacteriophage Capsid Head DNA Contractile Sheath Tail Tail Fibers Base Plate03/04/12 MASDIANA PADAGA 40
    41. 41. 03/04/12 MASDIANA PADAGA 41
    42. 42. Prions•Prions are “infectiousproteins”• They are normal bodyproteins that getconverted into an alternateconfiguration by contactwith other prion proteins• They have no DNA orRNA•The main protein involvedin human and mammalianprion diseases is called“PrP” 03/04/12 MASDIANA PADAGA 42
    43. 43. Prion Diseases•Prions form insolubledeposits in the brain•Causes neurons torapidly degeneration.•Mad cow disease (bovinespongiform encephalitis:BSE) is an example•People in New Guineaused to suffer fromkuru, which they gotfrom eating the brainsof their enemies 03/04/12 MASDIANA PADAGA 43

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