1. Chapter 6 Introduction to Viruses
Topics
Background
Structure
Classification
Multiplication
Cultivation and replication
Nonviral infectious agents
Treatment

2. Introduction and History
1884 Pasteur
-developed first vaccine for rabies
-proposed the term “virus” to denote this special
group
1892 Iwanowski & 1898 Beijerinck
- Discovered the fluids from infected tobacco plants could be filtered off all cells, but still remained contagious. Something smaller than bacteria was causing the tobacco mosaic disease.
-“Contagium vividium fluidium”
- “Filterable virus”
- “Virus” Latin for “poison” (virion)

3. 1935 – Biochemist Wendell Stanley
purified and crystallized tobacco mosaic
virus.
1940’s – With the advent of the electron microscope we could finally see viral shapes and sizes.

4. Characteristics of Viruses
Minuscule, acellular infectious agent
Causes many infections of humans, animals, plants, and bacteria
Causes most of the diseases that plague the industrialized world
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5. Viruses: Alive or not? Viruses have living & nonliving characters
DNA or RNA, not both
Obligate intracellular parasite
Can be crystallized
No growth or metabolism
No cell structure
Alive
Nucleic acids
Reproduction
Respond to stimuli
Evolve

6. Structure
Size and morphology
Capsid
Envelope
Complex
Nucleic acid

7. Structure of Viruses Size range -smallest infectious agents
-ultramicroscopic (<0.2 micrometers) an electron microscope is necessary to examine them.
- 2,000 bacteriophages could fit inside an average bacterial cell. 50 million poliovirus could fit in an average human cell.

9. Figure 13.4 Sizes of selected virions
E. coli (bacterium) (1000 nm  3000 nm)
Red blood cell (10,000 nm in diameter)
Bacterial ribosomes (25 nm)
Smallpox virus (200 nm  300 nm)
Poliovirus (30 nm)
Bacteriophage T4 (50 nm  225 nm)
Bacteriophage MS2 (24 nm)
Tobacco mosaic virus (15 nm  300 nm)

10. Viral structures - no cell structure so what is it?
- 3 possible pieces to viruses
1. Nucleic acid core – one or many strands of DNA
or RNA but not both
2. Capsid – protective outer shell made of
protein subunits called capsomeres
3. Envelope – optional, not all viruses have this.
Usually a modified piece of the hosts cell
membrane.

12. There are two major structures of viruses called the naked nucleocapsid virus and the enveloped virus.
Fig. 6.4 Generalized structure of viruses

13. Nucleic acid
Unlike cells, viruses contain either DNA or RNA, but not both
Possess only the genes to invade and regulate the metabolic activity of host cells
Ex. Hepatitis B (4 genes) and herpesviruses (100 genes)
No viral metabolic genes, as the virus uses the host’s metabolic resources

14. Nucleic acid core
- Viral Nucleic acids must contain instructions for at least 4 things
1. Genes for regulating the actions of the host
2. Genes for synthesizing the viral genetic
material
3. Genes for synthesizing the viral capsid and
proteins
4. Genes for assembling and packaging the
mature virus.

15. -Viruses only contain DNA or RNA but not both.
-Viruses may contain dsDNA*, ssDNA, dsRNA, and
ssRNA*.
-Gene numbers range from 4 in hepatitis B to
hundreds in herpesviruses. E. coli has 4,000 and
humans have 30-40,000.
-Some viruses will have a few enzymes like
polymerases, or in the case of HIV reverse
transcriptase for making DNA from RNA. Some
viruses will steal items from the host cell like
ribosomes or tRNA.

16. Figure 13.2 The relative sizes of genomes
Partial genome of E. coli
Viral genome

17. Characteristics of Viruses
Viral Shapes
Three basic shapes
Helical
Polyhedral
Complex
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18. Capsid Protective outer shell that surrounds viral nucleic acid
Capsid spikes
Composed of capsomer subunits
Two types of capsids
Helical
Icosahedral

19. Capsid-. protein coat surrounding nucleic acid core, made of
Capsid- protein coat surrounding nucleic acid core, made of identical subunits called capsomeres, that spontaneously self-assemble
Multiple shapes – either Icosahedral or Helical
- Icosahedron, 3 dimensional, 20 sided, with 12 evenly spaced corners

20. Icosahedron capsid
Three-dimensional, 20-sided with 12 evenly spaced corners
Variation in capsomer number
Polio virus 32 capsomers
Adenovirus 240 capsomers

22. Helical capsid Naked helical virus Enveloped helical virus
Ex. Tobacco mosaic virus
Nucleocapsid is rigid and tightly wound into a cylinder-shaped package
Enveloped helical virus
Ex. Influenza, measles, rabies
Nucleocapsid is more flexible

23. Helical tubular rod shaped capsomeres, bonded to form a series of hollow discs, then bound together to form a tube that resembles a bracelet.

24. Complex shape, a more intricate or varied structure
Poxviruses lack a capsid and instead has layers of lipoproteins and coarse surface fibers
Bacteriophages – combination of icosahedral and helical plus other pieces

25. Figure 13.6 Bacteriophage T4-overview

26. Enveloped vs. Naked viruses
- envelope usually made from the host’s cell membrane.
Many or all of the regular proteins are substituted with viral proteins.
Spikes are necessary for recognition and attachment to the next host cell.

27. Figure 13.7 Enveloped virion-overview

28. Icosahedral viruses can be naked or enveloped.
Fig. 6.8 Two types of icosahedral viruses

29. Envelope Lipid and proteins Envelope spikes
During release of animal viruses, a part of the host membrane is taken
Enable pleomorphic shape of the virus
Spherical
filamentous

30. Function of the capsid/envelope
Protection
The outer layer protects the virion (nucleic acid) from enzymes, and chemicals outside of the host cell. Example; intestinal viruses are resistant to acids and digestive enzymes in the GI tract.
Penetration of host cell
These outer layers bind to the host and assist in the insertion of the viral nucleic acid.
Activation of Immune system
Portions of the capsids and envelopes stimulate the immune system and produce antibodies for future infections.

31. Complex viruses
Structure is more intricate than helical and icosahedral viruses
Pox virus
Several layers of lipoproteins
Course surface fibrils
Bacteriophage
Polyhedral head
Helical tail
Fibers for attachment

32. Comparison of the morphology (helical, icosahedral, complex) of a naked virus, enveloped virus and a complex virus.
Fig. 6.9 Morphology of viruses

33. Examples of medically important DNA viruses.

34. Examples of medically important RNA viruses.

35. Classification Structure Chemical composition Genetic makeup
Host relationship
Type of disease

36. Three orders of viruses have been developed for classification.
Table 6.4 Examples from the three orders of viruses.

37. Classification of important human viruses.
Table 6.5 Important human virus families, genera, common names, and types of viruses.

38. Bacteriophages - Excellent example of virus multiplication cycle
- Bacteriophages are
viruses that attack bacteria.
- Discovered in 1915
- Culturing bacteriophages
on a lawn of bacteria they
form clear plaques
-example of T-even phage that infect E. Coli
- Reproduction of bacteriophages
can occur in two different cycles.

39. Viral Replication
Dependent on hosts’ organelles and enzymes to produce new virions
Lytic replication
Replication cycle usually results in death and lysis of host cell
Stages of lytic replication cycle
Attachment
Entry
Synthesis
Assembly
Release
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40. Lytic Cycle
1. Adsorption - Virus engages host cell by chance collision. Viruses do not move on their own.
2. Penetration – chemical interaction causes the contraction of the tail and it injects DNA into bacterial cell. Leaves ghost phage behind.

41. 3. Synthesis – the bacterial cell replicating viral DNA
3. Synthesis – the bacterial cell replicating viral DNA. Protein synthesis is taking place making capsids, proteins, and nuclease.
*Nuclease destroys bacterial DNA so
host has only viral DNA.
4. Assembly and maturation – viral parts come together, chemical reactions bring and glue pieces together.

42. Release by lysis – Lysozyme is used to lyse the host bacterial cells, this allows viruses to escape. We also have lysozyme in our own mucous secretions it helps keep us clear of bacterial infection.
Burst time – average min. to go from
penetration to release.
Burst size – viruses per cell burst.

43. Lytic cycle

44. Viral Replication Lysogeny Modified replication cycle
Infected host cells grow and reproduce normally for generations before they lyse
Temperate phages
Prophages – inactive phages
Lysogenic conversion results when phages carry genes that alter phenotype of a bacterium
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45. Lysogenic Cycle. - will not kill host immediately and results in
Lysogenic Cycle - will not kill host immediately and results in viral persistence - performed by temporate phages
1. Adsorption –Virus engages host cell by chance collision. Viruses do not move on their own.
2. Penetration – chemical interaction causes the contraction of the tail and it injects DNA into bacterial cell. Leaves ghost phage behind.
3. Lysogenic conversion – the bacteriophage DNA is integrated into the bacterial DNA. As the cell goes through binary fission, the bacteriophage DNA is copied with it.

46. 4.Excision – Due to environmental stimulus the prophage comes out of bacterial DNA, takes over the cell, and the lytic phase of the cycle begins.
5. Synthesis
6. Assembly
7. Release
by lysis.

47. Figure 13.17 Viral plaques in a lawn of bacterial growth on the surface of an agar plate
Bacterial lawn
Viral plaques

48. Lysogenic Cycle

49. Lysogenized conversion
– bacterial cell has been changed because
Viral DNA has been added to the bacterial
DNA
- bacterium acquires new traits from its temporate phage
Streptococcus pyogenes – If it’s lysogenized ‘strep’ it can result in scarlet fever.
2. Corynebacterium diptheriae – Lysogenized bacteria will result in diptheria, non lysogenized, it’s harmless.

50. Animal viruses
Bacteriophages are a nice general model for the workings of viruses however animal viruses do a few things differently.
A. Host range
B. Method of penetration
C. How/where the nucleic acid works in the host
D. Method of leaving the host cell.

52. Host range
An exact fit between virus spikes and cell receptors is needed in order for
adsorption to occur.
this means the number of cells it can infect is limited, this is known as host range.
Spectrum: hepatitis B infects only human liver cells, Poliovirues infects primate intestinal and nerve cells, and rabies virus infects various cells in all mammals.

53. Method of penetration
In bacteriophages, we have ghost phages left behind after penetration of nucleic acids.
Animal viruses can either enter the cell as the whole virion through endocytosis, or it only introduces its nucleic acid by membrane fusion.

54. In penetration by endocytosis the whole virus is engulfed by the host cell.
It is enclosed in a vacuole
Enzymes in the vacuole dissolves the envelope and capsid, this is called uncoating.

55. Entry by membrane fusion involves the virus simply merging with the host cells membrane and uncoating at the same time.

56. Uncoating step
Host cell membrane
Free
DNA
Virus in
vesicle
Vesicle, envelope
and capsid break
down
Specific
attachment
Engulfment
(a)
Host cell
membrane
Free
RNA
Receptors
Uncoating
of nucleic
acid
RNA
Spike
Envelope
Receptor-
spike complex
Entry of
nucleocapsid
Irreversible
attachment
Membrane
fusion
(b)

57. How/where the nucleic acid is working
Once the viral nucleic acid gets into the host cell depending on what type of nucleic acid it is, it will begin work in either the nucleus or the cytoplasm.
-DNA viruses enter the host cell nucleus and are replicated and assembled there
-RNA viruses are replicated and assembled in the cytoplasm. Some have positive sense strands and some have negative sense strands.
-Retroviruses are a little different

58. Uncoating and synthesis of viruses rely on the host’s metabolic systems.
Fig General feature in the multiplication
cycle of an enveloped animal virus.

59. Different forms of viral nucleic acids arrive in the cell and accomplish their tasks by different methods!!!

60. Method of leaving the host cell
While bacteriophages generally always lyse the bacterial cell they infect, animal viruses, are not so predictable.
- Non-enveloped and complex viruses will
lyse or rupture the host cell.
- Enveloped viruses are released by budding,
also known as exocytosis (or budding).

61. The process of exocytosis begins with the nucleocapsid binds to the membrane
The membrane forms a pouch and then that pouch pinches off the host cell and forms the envelope.
This is a gradual process of shedding viruses.

63. Figure 13.14 The process of budding in enveloped viruses
Enveloped virion
Budding of enveloped virus
Viral glycoproteins
Cytoplasmic membrane of host
Viral capsid

64. After effects of viral infection
No matter how the virus leaves the cell, irreversible damage has occurred and is ultimately lethal due to damage to metabolism, organelles, and cell membrane.
Burst size for animal cells range from 3-4,000 for pox viruses to 100,000+ for polioviruses

65. Cytopathic effects Damage to the host cell due to a viral infection
Inclusion bodies
Syncytia
Chronic latent state
Transformation

66. Examples of syncytia and inclusion bodies.
Fig Cytopathic changes in cells and cell
cultures infected by viruses

67. Latency
Some cells maintain a carrier relationship with the infecting virus
The cell harbors the virus and is not immediately lysed, these are considered persistent infections and can last from a few weeks to lifelong.
Several viruses remain in a chronic latent state, meaning they are inactive over long periods of time. Herpes simplex virus and herpes zoster virus go into latency in nervous tissue and reappear due to stimuli. When animal viruses remain dormant in host cells
Some latent viruses do not become incorporated into host chromosome
Incorporation of provirus into host DNA is permanent

68. Oncoviruses
Some animal viruses permanently alter that cells genetic material, leading to cancer.
The effect on those cells is called transformation, the viral nucleic acid is consolidated into the host DNA
Transformed cells have increased growth, chromosomal alteration, cell surface alteration, and indefinite cell division.

69. Other noncellular infectious agents
Prions
- small protein fibrils found deposited in the brain tissue of animals infected with spongiform encephalopathies.
Prions are composed
primarily of protein
(no nucelic acids).
Thought that proteins
meet up with existing
prions and “shape flip” to
match.

70. Diseases Caused By Prions
1) Creutzfeld-Jakob Disease
- Affects the nervous system, gradual degeneration and death.
- Transmissible but mechanism unknown.
2) Bovine spongiform encephalopathy, or “mad cow disease”
Can be acquired by consumption of contaminated beef
First incidence of prion disease transmission from animal to human.
With Both Diseases:
- Infections have a long period of latency (several years).
- Signs include mental derangement, loss of muscle control. Diseases are
progressive and universally fatal.

71. Satellite viruses
Viruses that are dependent on other viruses for replication
AAV, adeno associated virus. Replicates only in cells infected with adenovirus.
2. Delta agent, a naked strand of RNA expressed only in the presence of hepatitis B virus.

72. Treatment of viral infections
The uncommon nature of viruses make them difficult to deal with
Many antiviral drugs block viral replication by blocking host cell function. Leads to severe side effects.
Azidothymide (AZT) targets the synthesis stage of the life cycle.
Protease inhibitors interrupt the assembly phase.

73. Antiviral drugs
Selective toxicity is almost impossible to achieve with viruses. Why?
Three major modes of viral drug actions are:
1. Halting penetration of virus into host cell
2. Blocking transcription and/or translation
3. Preventing assembly, or maturation of viral pieces
Antiviral drugs protect uninfected cells, but don’t do much for extracellular viruses or latent viruses

76. Interferon Natural method of virus control is interferon.
At first limited by the limited quantities acquired from blood. Now produced by recombinant DNA technology.

77. Interferon benefits include:
Reducing time in healing and complications of certain infections
Preventing/reducing symptoms of cold and papillomaviruses
Slowing certain cancers, bone, cervical, certain leukemias and lymphomas
Treating hepatitis C, genital warts, Kaposi’s sarcoma, and a rare cancer; hairy-cell leukemia