Chapter 10 Lecture
- 1. Overview of Viruses and Virology Chapter 10 Lectures by Buchan & LeCleir
- 2. I. Virus Structure and Growth 10.1 General Properties of Viruses 10.2 Nature of the Virion 10.3 The Virus Host 10.4 Quantification of Viruses
- 3. 10.1 General Properties of Viruses Virus : genetic element that cannot replicate independently of a living (host) cell Virology : the study of viruses Virus particle : extracellular form of a virus; allows virus to exist outside host and facilitates transmission from one host cell to another Virion : the infectious virus particle; the nucleic acid genome surrounded by a protein coat and, in some cases, other layers of material
- 4. 10.1 General Properties of Viruses Viral Genomes Either DNA or RNA genomes Some circular, but most linear
- 5. Viral Genomes Figure 10.1
- 6. 10.1 General Properties of Viruses Viral Hosts and Taxonomy Viruses can be classified on the basis of the hosts they infect Bacterial viruses (bacteriophages) Animal viruses Plant viruses
- 7. 10.2 Nature of the Virion Most viruses are smaller than prokaryotic cells; range from 0.02 to 0.3 µm Most viral genomes are smaller than those of biological cells
- 8. 10.2 Nature of the Virion Viral Structure Capsid : the protein shell that surrounds the genome of a virus particle Composed of a number of protein molecules arranged in a precise and highly repetitive pattern around the nucleic acid Capsomer : subunit of the capsid Smallest morphological unit visible with an electron microscope
- 9. 10.2 Nature of the Virion Viral Structure (cont’d) Nucleocapsid : complete complex of nucleic acid and protein packaged in the virion Enveloped virus : virus that contains additional layers around the nucleocapsid
- 10. Comparison of Naked and Enveloped Virus Particles Figure 10.3
- 11. 10.2 Nature of the Virion N ucleocapsids of viruses constructed in highly symmetric ways Helical symmetry : rod-shaped viruses (e.g., tobacco mosaic virus) Length of virus determined by length of nucleic acid Width of virus determined by size and packaging of protein subunits Icosahedral symmetry : spherical viruses Most efficient arrangement of subunits in a closed shell
- 12. Icosahedral Symmetry Figure 10.4
- 13. Icosahedral Symmetry Figure 10.4
- 14. 10.2 Nature of the Virion Enveloped Viruses Have membrane surrounding nucleocapsid; lipid bilayer with embedded proteins Make initial contact with host cell
- 15. Electron Micrographs of Animal and Bacterial Viruses Figure 10.5
- 16. 10.2 Nature of the Virion Complex Viruses Virions composed of several parts, each with separate shapes and symmetries Examples of most complex viruses in terms of structure can be found among bacterial viruses, which contain icosahedral heads and helical tails
- 17. 10.2 Nature of the Virion Some virions contain enzymes critical to infection Lysozyme Nucleic acid polymerases Neuraminadases : enzymes that cleave gycosidic bonds; allows liberation of viruses from host
- 18. 10.3 The Virus Host Viruses replicate only in certain types of cells or in whole organisms Bacterial viruses are typically easiest to grow; model systems Animal viruses (and some plant viruses) can be cultivated in tissue or cell cultures Plant viruses typically are most difficult because study often requires growth of whole plant
- 19. 10.4 Quantification of Viruses Titer : number of infectious units per volume of fluid Plaque assay : analogous to the bacterial colony; one of the most accurate ways to measure virus infectivity Plaques are clear zones that develop on lawns of host cells Each plaque results from infection by a single virus particle
- 20. Quantification of Bacterial Virus by Plaque Assay Figure 10.6
- 21. Quantification of Bacterial Virus by Plaque Assay Figure 10.6
- 22. 10.4 Quantification of Viruses The number of plaque-forming units is almost always lower than direct counts by microscopy Inactive virions Conditions not appropriate for infectivity
- 23. II. Viral Replication 10.5 General Features of Virus Replication 10.6 Viral Attachment and Penetration 10.7 Production of Viral Nucleic Acid and Protein
- 24. 10.5 General Features of Virus Replication The Phases of Viral Replication Attachment (adsorption) of the virus to a susceptible host cell Entry (penetration) of the virion or its nucleic acid Synthesis of virus nucleic acid and protein by cell metabolism as redirected by virus Assembly of capsids and packaging of viral genomes into new virions (maturation) Release of mature virions from host cell
- 25. The Replication Cycle of a Bacterial Virus Figure 10.8
- 26. 10.5 General Features of Virus Replication Virus replication typically characterized by a one-step growth curve Latent period : eclipse + maturation Burst size : number of virions released
- 27. The One-Step Growth Curve of Virus Replication Figure 10.9
- 28. 10.6 Viral Attachment and Penetration Attachment of virion to host cell is highly specific Requires complementary receptors on the surface of a susceptible host and its infecting virus Receptors on host cell carry out normal functions for cell (e.g., uptake proteins) Receptors include proteins, carbohydrates, glycoproteins, lipids, lipoproteins, or complexes
- 29. 10.6 Viral Attachment and Penetration The attachment of a virus to its host cell results in changes to both virus and cell surface that facilitate penetration Permissive cell : host cell that allows the complete replication cycle of a virus to occur
- 30. 10.6 Viral Attachment and Penetration Bacteriophage T4 : virus of E. coli ; example of one of the most complex penetration mechanisms known Virions attach to cells via tail fibers that interact specifically with polysaccharides on E. coli cell envelope Tail fibers retract and tail core makes contact with E. coli cell wall Lysozyme-like enzyme forms small pore in peptidoglycan Tail sheath contracts and viral DNA passes into cytoplasm
- 31. Attachment of Bacteriophage T4 to the Cell Wall of E. coli Figure 10.10
- 32. 10.6 Viral Attachment and Penetration Many eukaryotes possess mechanisms to diminish viral infections E.g., immune defense mechanisms, RNA interference
- 33. 10.6 Viral Attachment and Penetration Many bacteria employ restriction-modification systems to evade viral infection DNA destruction system; only effective against double-stranded DNA viruses Restriction enzymes (restriction endonucleases) cleave DNA at specific sequences Modification of host’s own DNA at restriction enzyme recognition sites prevent cleavage of own DNA
- 34. 10.6 Viral Attachment and Penetration Viral mechanisms to evade bacterial restriction systems Chemical modification of viral DNA (glycosylation or methylation) Production of proteins that inhibit host cell restriction system
- 35. 10.7 Production of Viral Nucleic Acid and Protein David Baltimore, Howard Temin, and Renato Dulbecco discovered retroviruses and reverse transcriptase Shared 1975 Nobel Prize for Physiology or Medicine Baltimore developed classification scheme for viruses based on relationship of viral genome to its mRNA
- 36. The Baltimore Classification System of Viruses
- 37. 10.7 Production of Viral Nucleic Acid and Protein Once a host has been infected, new copies of the viral genome must be made and virus-specific proteins synthesized in order for the virus to replicate Generation of messenger RNA (mRNA) occurs first Typically viral genome serves as template for viral mRNA In some RNA viruses, viral RNA itself is the mRNA In some cases essential transcriptional enzymes are contained in the virion
- 38. 10.7 Production of Viral Nucleic Acid and Protein Retroviruses : animal viruses responsible for causing certain types of cancers and acquired immunodeficiency syndrome (AIDS) Class VI and VII viruses Require reverse transcriptase
- 39. 10.7 Production of Viral Nucleic Acid and Protein Viral Proteins Production follows synthesis of viral mRNA Early proteins synthesized soon after infection necessary for replication of virus nucleic acid typically act catalytically synthesized in smaller amounts
- 40. 10.7 Production of Viral Nucleic Acid and Protein Production of Viral Proteins (cont’d) Late proteins Synthesized later Include proteins of virus coat Typically structural components Synthesized in larger amounts
- 41. III. Viral Diversity 10.8 Overview of Bacterial Viruses 10.9 Virulent Bacteriophages and T4 10.10 Temperate Bacteriophages, Lambda, and P1 10.11 Overview of Animal Viruses 10.12 Retroviruses
- 42. 10.8 Overview of Bacterial Viruses Bacteriophages are very diverse Best-studied bacteriophages infect enteric bacteria E.g., E. coli , Salmonella enterica Most contain dsDNA genomes Most are naked, but some possess lipid envelopes They are structurally complex, containing heads, tails and other components
- 43. 10.8 Overview of Bacterial Viruses Viral Life Cycles Virulent mode : viruses lyse host cells after infection Temperate mode : viruses replicate their genomes in tandem with host genome and without killing host
- 44. 10.10 Temperate Bacteriophages, Lambda, and P1 Temperate viruses : can undergo a different life cycle resulting in a stable genetic relationship within the host But can also kill cells through lytic cycle Lysogeny : state where most virus genes not expressed and virus genome ( prophage ) is replicated in synchrony with host chromosome Lysogen : a bacterium containing a prophage Under certain conditions lysogenic viruses may revert to the lytic pathway and begin to produce virions
- 45. The Consequences of Infection by a Temperate Phage Figure 10.16
- 46. 10.10 Temperate Bacteriophages, Lambda, and P1 Bacteriophage Lambda Linear, dsDNA genome Complementary, single-stranded regions 12 nucleotides long at the 5 ′ -terminus of each strand Upon penetration, DNA ends base-pair forming the cos site, DNA ligates and forms double-stranded circle When lysogenic, integrates into E. coli chromosome at the lambda attachment site ( att
- 47. Bacteriophage Lambda Figure 10.17
- 48. Integration of Lambda DNA into the Host Figure 10.18
- 49. 10.11 Overview of Animal Viruses Unlike prokaryotes, entire virion enters the animal cell Eukaryotic cells contain a nucleus, the site of replication for many animal viruses Animal viruses contain all known modes of viral genome replication Many more kinds of enveloped animal viruses than bacterial viruses exist As animal viruses leave host cell, they can remove part of host cell’s lipid bilayer for their envelope
- 50. Diversity of Animal Viruses: DNA Viruses Figure 10.21a
- 51. Diversity of Animal Viruses: RNA Viruses Figure 10.21b
- 52. 10.11 Overview of Animal Viruses Consequences of Virus Infection in Animal Cells Persistent infections : release of virions from host cell does not result in cell lysis Infected cell remains alive and continues to produce virus indefinitely Latent infections : delay between infection by the virus and lytic events Transformation : conversion of normal cell into tumor cell
- 53. 10.12 Retroviruses Retroviruses : RNA viruses that replicate through a DNA intermediate Enveloped viruses Contain a reverse transcriptase (copies information from its RNA genome into DNA), integrase, and protease Virion contains specific tRNA molecules
- 54. Retrovirus Structure and Function Figure 10.23a
- 55. 10.12 Retroviruses Retroviruses have a unique genome Two identical ssRNA molecules of the plus (+) orientation Contain specific genes gag : encode structural proteins pol : encode reverse transcriptase and integrase env : encode envelope proteins
- 56. 10.12 Retroviruses Process of Replication of a Retrovirus Entrance into the cell Removal of virion envelope at the membrane Reverse transcription of one of the two RNA genomes Integration of retroviral DNA into host genome Transcription of retroviral DNA Assembly and packaging of genomic RNA Budding of enveloped virions; release from cell
- 57. Replication Process of a Retrovirus Figure 10.24
- 58. IV. Subviral Entities 10.13 Defective Viruses 10.14 Viroids 10.15 Prions
- 59. 10.13 Defective Viruses Helper viruses (defective viruses) : viruses that are parasitic on other viruses Satellite viruses : defective viruses for which no intact version exists; rely on unrelated viruses as helpers
- 60. 10.14 Viroids Viroids : infectious RNA molecules that lack a protein coat Small, circular, ssRNA molecules Smallest known pathogens (246–399 bp) Cause a number of important plant diseases Do not encode proteins; completely dependent on host-encoded enzymes
- 61. Viroids and Plant Disease: Healthy vs. PSTV-Infected Figure 10.25
- 62. 10.15 Prions Prions : infectious proteins whose extracellular form contains no nucleic acid Known to cause disease in animals (transmissible spongiform encephalopathies) Host cell contains gene ( PrnP ) that encodes native form of prion protein that is found in healthy animals Prion misfolding results in neurological symptoms of disease (e.g., resistance to proteases, insolubilty, and aggregation)
- 63. Mechanisms of Prion Misfolding Figure 10.28
- 64. 10.15 Prions Prion disease occurs by three distinct mechanisms Infectious prion disease : pathogenic form of prion protein is transmitted between animals or humans Sporadic prion disease : random misfolding of a normal, healthy prion protein in an uninfected individual Inherited prion disease : mutation in prion gene yields a protein that changes more often into disease-causing form