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Medical Microbiology

Medical Microbiology. Li Mei Department of Microbiology November, 2006. Virology. Chapter 19. General Properties of Viruses. Structure Replication. Viruses the smallest infectious and acellular microbe consisting only one kind of nucleic acid (DNA or

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Medical Microbiology

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  1. Medical Microbiology Li Mei Department of Microbiology November, 2006

  2. Virology

  3. Chapter 19 General Properties of Viruses Structure Replication

  4. Viruses the smallest infectious and acellular microbe consisting only one kind of nucleic acid (DNA or RNA), and which obligately replicate inside host cells. What is virus? • Virions The complete mature viral particles. (The intact infectious virus particles.)

  5. Acellular microbes Pass through 0.2μm filters Obligatory intracellular parasites. Contain either DNA or RNA Self-replication Distinctive features

  6. A.Size: The unit of measurement poxviruses parvoviruses I. Size, shape and structure nm

  7. Comparative sizes of virions and bacteria • 1. Staphylococcus aureus • 2. Rickettsia • 3. Chlamydia • 4. Poxviruses • 5. Bacteriophage of E. coli • 6. Influenza virus • 7. Adenovirus • 8. Encephalitis B virus • 9. Poliovirus

  8. I. Size, shape and structure B. Shape:

  9. Tobacco mosaic virus: rod-shaped

  10. Poxvirus: brick-shaped

  11. HIVSpherical

  12. VSV (Vesicular stomatitis virus):bullet-shaped

  13. Bacteriophage T4: tadpole-shaped

  14. Ebola Virus: filamentous shape

  15. I. Size, shape and structure C.Structure: • Basic structure: • Core:Viral nucleic acid (DNA or RNA) • Capsid: Protein shell • capsomers(morphological subunit) • polypeptide molecules (chemical subunit) Core + Capsid → nucleocapsid

  16. I. Size, shape and structure • Naked virus: • Virion: nucleocapsid. • Enveloped virus: • Virion: nucleocapsid+Envelope • spikes (peplomers); Others: enzymes, etc. e.g. Retrovirus has reverse transcriptase

  17. Influenza virus HA - hemagglutinin NA - neuraminidase nucleocapsid lipid bilayer envelope

  18. I. Size, shape and structure 2. Symmetry of viral nucleocapsids -- is decided by arrangement of capsomers • Helical symmetry (e.g., tobacco mosaic virus) • Icosahedral symmetry (e.g., adenovirus) • Complex symmetry (e.g., poxviruses )

  19. Influenza virus

  20. Viroid plant disease Human Hepatitis D Prion Proteinaceous infectious particle Human diseases: e.g., Kuru Creutzfeldt-Jakob disease(CJD) Gerstmann-Straussler-Scheinker Syndrome (GSS) Fatal Familial Insomnia (FFI) Animal diseases: e.g., Scrapie Bovine spongiform encephalopathy (BSE) a single circular RNA molecule without a protein coat which mainly cause plant diseases. infectious agents composed of a single glycoprotein with MW 27-30 kDa. Unconventional viruses

  21. II. Replication In host cell, virusreplicates its nucleic acid and synthesizes its proteins, then assembles them to form progeny viral particles that are released by budding or cell lysis.

  22. II. Replication A. Normal Replication • Adsorption /Attachment • Penetration • Uncoating • Biosynthesis • Assembly • Release

  23. II. Replication • Attachment / Adsorption

  24. Attachment / Adsorption

  25. Mechanisms: A.Endocytosis II. Replication • Penetration

  26. B.Fusionbetween cell membrane and viral envelope The enveloped viruses II. Replication

  27. C. Nucleic acid translocation: Somebacteriophages and naked viruses II. Replication

  28. penetration

  29. outside inner A B C D

  30. Uncoating: The process that capsid is removed and viral nucleic acid is released in the host cell. II. Replication • Biosynthesis: Eclipse phase Biosynthesis includes: Viral genome replication Viral protein synthesis • Types: dsDNA, ssDNA, dsRNA, +ssRNA, -ssRNA, Retrovirus

  31. early proteins (nonstructural proteins) Biosynthesis dsDNA viruses:e.g., Herpes simplex virus Cell’s DDRP early mRNA dsDNA (template) DDDP semi-conservative replication progeny viral DNA late mRNA late proteins (structural proteins) assembly progeny viral nucleocapsid

  32. (+) ssRNA Translation (-) ssRNA Replication Release Cleavage Assembly RNA polymerase Viral proteins Structural protein Examples: Poliovirus, HAV +ssRNA virus

  33. -ssRNA virus e.g., influenza virus RNA Polymerase Transcription Translation RNA Polymerase Structural protein

  34. Assembly Naked virus: capsid + viral genome → nucleocapsid (virion) II. Replication Enveloped virus: nucleocapsid + envelope → virion Site: a. DNA viruses (except poxvirus):cell nucleus; b.RNA viruses and poxvirus: cell cytoplasm; Manner: a. assemble as empty shell (procapsids), then viral genome fill in. b. Viral capsomers array around the viral genome to form helical symmetry.

  35. Release The process of progeny viruses getting out of host cell. Naked viruses: released by cell lysis. Enveloped viruses: usually released by budding. During budding enveloped viruses acquire their envelope. Defective measles virus: release from cell to cell viacell bridges.  SSPE (Subacute sclerosing panencephalitis) II. Replication

  36. Host cell lysis Budding

  37. release

  38. B. Abnormal replication: Defective viruses Abortive infection II. Replication

  39. Defective viruses: are genetically deficient and incapable of producing infectious progeny virions. Helper virus: can supplement the genetic deficiency and make defective viruses replicate progeny virions when they simultaneously infect host cell with defective viruses. II. Replication e.g., AAV & adenovirus

  40. Defective Viruses lack gene(s) necessary for a complete infectious cycle helper viruses provide missing functions A genome B A B Defective Viruses

  41. DIP: Defective viruses which can occupy the cell machinery necessary for normal virus replication to prevent virus production, are called "defective interfering particles" (DIP). Defective interfering particles (DIP)

  42. 2. Abortive infection: Virus infection which does not produce infectious progeny because the host cell cannot provide the enzyme, energy or materials required for the viral replication. non-permissive cells The host cells that cannot provide the conditions for viral replication. permissive cells The host cells that can provide the conditions for viral replication. II. Replication

  43. Viral interference When two viruses infect simultaneouslyone host cell, the virus A may inhibit replication of virus B. Range of interference occurrence between the different species of viruses; between the same species of viruses; between the inactivated viruses and live viruses. III. Viral interference:

  44. Mechanisms of viral interference: a.Virus A may inhibit virus B adsorption by blocking or destroying receptors on host cell. b.Virus A may compete with virus B for replication materials like polymerase, translation initiation factors, etc. c.Virus A may induce the infected cell to produce interferon that can prevent viral replication. III. Viral interference

  45. Significance of interference: Advantage a. Stop viral replication and lead to patient recovery. b. Inactivated virus or live attenuated virus can be used as vaccine to interfere with the infection of the virulent virus. Disadvantage May decrease the function of vaccine when bivalent/trivalent vaccine is used. III. Viral interference:

  46. Physical agents: Temperature, pH, Irradiation Chemicals: Phenol and its derivatives; Formaldehyde/formalin; 70% ethanol; Oxidizing agents; Lipid solvents; Biological agents Antibiotic, interferon, etc. IV. Reaction to physical & chemical agents -196℃

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