1. Viruses

2. Egyptian stele (1580-1350 B.C) Crippled priest
Egyptian stele dating from the 18th Dynasty ( BC). A crippled young man, apparently a priest, is pictured with a withered and shortened left leg, with his foot in the typical equinus position characteristic of flaccid paralysis; his staff is apparently being used as a support.
Carlsberg Glyphotheke, Copenhagen.

3. Poxviruses (Poxviridae)
The Pharaoh Ramses V died of smallpox (variola virus) in 1157 B.C.
In 1520: million Aztecs died
Last case in Somalia on 26th October 1977
Sept.11—variola virus as a bioterrorism weapon?
Don’t confuse with chickenpox (varicella)

4. VIRUSES Virus = Latin for poison Isolation of the first Virus
Dmitri Iwanowski in 1892
Tobacco mosaic virus which affects >150 plants world wide stunted growth
“filterable agent”
                               2

5. VIRUSES, LIVING ORGANISMS?
Life=A complex set of processes resulting from the actions of proteins specified by nucleic acids
Viruses:
Inert outside host cells
Obligate intracellular parasites
Do not divide 3

6. VIRION A complete, fully developed viral particle
Virions are the transmissible state of a virus. Metabolically inert
Virions must be able to adhere and allow entry into some host cell(s)
Also to survive outside of host cell environment.
Some virions more hardy than others (hepatitis virus A can withstand short periods of boiling; most virions are destroyed by this) 4

7. VIRUS SIZE Most, 20 to 300 nm (0.02 to 0.3 mm)
Filoviruses up to 14,000 nm
Exceptional 13

9. Only one type of nucleic acid (NA) DNA or RNA
STRUCTURE OF VIRUSES
Only one type of nucleic acid (NA)
DNA or RNA
NA enclosed by a protein coat 5

10. Types of viral nucleic acids
Circular
Linear
Segmented

11. Protein subunits, building blocks of the viral capsid
VIRAL CAPSOMERS
Protein subunits, building blocks of the viral capsid 15

12. Capsid composed of repeating subunits - capsomers
STRUCTURE OF VIRUSES
Capsid composed of repeating subunits - capsomers
helical, icosahedral, complex
protection, attachment, 8

13. Part of host’s cell membrane
ENVELOPED VIRUSES
Envelope present
Part of host’s cell membrane 9

14. Structure of Viruses
Envelope derived from host membrane lipids and virus proteins
nuclear, plasma membrane by budding
necessary for attachment

15. Nucleic
acid
Capsid
Envelope

16. 26

17. 25

18. NONENVELOPED OR NAKED VIRUSES
Envelope absent
More resistant than enveloped viruses 10

19. "Naked" viruses require host death so viruses can be released
Enveloped viruses: are shed virus particles ; they shed by budding out, continued release from cell membrane
Cell does not die (immediately), continues to serve as factory for virus assembly and release. Virus typically acquires a coating of host cell membrane, and will include virus-specific proteins. This is the "envelope"

20. Examples of enveloped viruses include:
Retrovirus, I.e. HIV
Paramyxovirus, I.e. influenza
Rhabdovirus, I.e. rabies
Enveloped Herpes virus

21. Naked virus
(no envelope)
Nucleic
acid
Capsid

22. Bacteriophages (Virus that infects Bacteria)
TYPES OF VIRUSES
Animal viruses
Plant viruses
Bacteriophages (Virus that infects Bacteria)
Ex: Coliphage infect E.coli cells 7

23. Types of Viral Infections
Oncogenic viruses
Herpes viruses

24. Multiply using the machinery of the host cell Have few or no enzymes
VIRAL METABOLISM
Multiply using the machinery of the host cell
Have few or no enzymes 11

25. HOST RANGE Species specific Small pox virus, humans Broad host range
Rabies virus, mammals 12

26. VIRAL SPIKES
Carbohydrate/protein complexes embedded in the viral envelope
Used as means of identification
Influenza virus, avian flue (H5N1)/Adenovirus 16

27. Adenovirus spikes Respiratory Illness, Common Cold,
“Pink Eye”, Gastrointestinal Illness

28. Cylindrical capsid with a helical structure Polyhedral
VIRAL MORPHOLOGY
Helical
Cylindrical capsid with a helical structure
Polyhedral
Icosahedral (20 triangular faces and 12 corners) 17

29. Helical nucleocapsid

30. RHABDOVIRUS 20

31. POLYHEDRAL

32. VIRAL MORPHOLOGY (cont.)
Complex viruses
Structures attached to capsid
Tail, tail fibers
Bacteriophages 22

33. Tail
Bacteriophage 23

34. POXVIRUS
Infections due to the poxviruses (members of the Poxviridae family) occur in humans and animals.
The orthopoxviruses include smallpox (variola), monkeypox, vaccinia, and cowpox viruses. 29

35. CLASSIFICATION OF ANIMAL VIRUSES
Type of nucleic acid
DNA or RNA
Single stranded (ss) or double stranded (ds)
Presence of envelope 25

36. CLASSIFICATION OF ANIMAL VIRUSES
Strategy for Replication
Where do they replicate?
Morphology
Structures
Described by common Names
Where is their niche? (Enteroviruses)

37. Classification of viruses

38. CLASSIFICATION OF ANIMAL VIRUSES (cont.)
ssDNA, nonenveloped
Parvovirus (Parvovirus B19 Fetal Death, GI)
dsDNA, nonenveloped
Adenovirus (Respiratory, GI)
Papovavirus (Warts, Tumors) 27

39. CLASSIFICATION OF ANIMAL VIRUSES (cont.)
dsDNA, enveloped
Poxvirus (Smallpox, Cowpox)
Herpesvirus (Fever blisters, Chicken pox, Shingles, Mononucleosis)
Hepadnavirus (Hepatitis B, Tumors) 28

40. HERPESVIRUS 30

41. CLASSIFICATION OF ANIMAL VIRUSES (cont.)
ssRNA, nonenveloped
Picornavirus (Polio, Common Cold, GI)
dsRNA nonenveloped
Reovirus (GI, Respiratory)
dsRNA enveloped
Retrovirus (Tumors, AIDS) 31

42. POLIOVIRUS 32

43. Polivirus structure 33

44. REOVIRUS
Reoviruses are infectious agents of the virus family Reoviridae, transmitted by respiratory and fecal-oral routes. They are not major human pathogens
reo (for respiratory, enteric, and orphan, the latter meaning not associated with human disease) 34

45. RETROVIRUS
They are enveloped viruses, with an RNA genome. The name is derived from the fact that the virus particle contains an RNA-dependent DNA Polymerase (Reverse transcriptase)
This enzyme converts the RNA genome into DNA, which then integrates into the host chromosomal DNA. The reverse transcriptase is highly error prone and rapid genetic variation is a feature of this group 35

46. CLASSIFICATION OF ANIMAL VIRUSES (cont.)
ssRNA, enveloped
Togavirus (Encephalitis)
Flavivirus (Dengue Fever, Yellow Fever, West Nile Virus)
Coronavirus (Common Cold)
Rhabdovirus (Rabies) 36

47. CORONAVIRUS 37

48. CLASSIFICATION OF ANIMAL VIRUSES (cont.)
ssRNA, enveloped
Filovirus (Ebola, Marburg)
Arenavirus (Hemorrhagic Fever)
Paramyxovirus (Mumps)
Orthomyxovirus (Influenza)
Bunyavirus (Hantavirus) 38

49. FILOVIRUS Marburg and Ebola virus Filo = threadlike
Appear in many different shapes (pleomorphic)
First ID in Germany/Yugoslavia from tissues of green monkeys who developed hemorrhagic fever
Filo = threadlike
Filovirus. Although very "hot" in the news, these viruses are very poorly characterized because of their extreme pathogenicity. They are class IV pathogens, meaning they can only be cultured in total containment facilities, of which there are only two in the U. S. They are thought to be enveloped viruses with - RNA genomes. 39

50. PART II

51. GROWTH OF VIRUSES Bacteriophages Bacterial cells Animal viruses
Animal cells
Animals and embryos 40

52. Growing Viruses Animal Viruses A. Living Animals
mice, rabbits, guinea pigs
B. Chicken Embryos (Eggs)
used to be most common method to grow viruses
Still used to produce many vaccines (Flu Vaccine)
C. Cell Cultures
Most common method to grow viruses today

53. PLAQUE ASSAY 52

54. LIVING ANIMALS
Diagnostic
Vaccine research
Expensive
Regulated 41

55. NEWBORN MOUSE 42

56. EMBRYONATED EGGS Diagnostic Vaccine production Inexpensive Unregulated43

57. CHIKEN EMBRYO 44

58. CHIKEN EMBRYO 45

59. CHICKEN EMBRYO 46

60. Derived from animals, or humans Culture in special medium
ANIMAL CELL CULTURES
Derived from animals, or humans
Culture in special medium
Infected cells show cytopathic effect (CPE) 48

61. Infected
monkey cells
Non-infected
monkey cells 49

62. Multinucleated (giant) cells infected with reovirus50

63. INCLUSION BODIES POX VIRUS51

64. ANIMAL CELL CULTURES Primary cell lines Tissues Diploid cell lines
Human embryos
Continuous cell lines
Cancerous cells 53

65. dedicated to the memory of Mrs. Henrietta Lacks, whose very cells,
“...This lecture is
dedicated to the memory
of Mrs. Henrietta Lacks,
whose very cells,
after her death,
have helped scientist all
around the world to find
ways to alleviate suffering
and prevent disease among all of us, who are still here...”

67. VIRAL IDENTIFICATION METHODS
Electron microscopy
Serological
Specific antibodies
Molecular biology
Nucleic acid sequences 54

69. VIRAL MULTIPLICATION Viral genes Viral proteins
A few enzymes (if any) usually involved with viral nucleic acid replication 56

70. VIRAL MULTIPLICATION (cont.)
Infected cell provides:
Enzymes and machinery for viral nucleic acid and protein synthesis
Energy 57

74. BACTERIOPHAGE MULTIPLICATION
Lytic cycle (lytic phages)
Lysis and death of host cell
Lysogenic cycle (Lysogenic or temperate phages)
Host cell carries phage NA and divides normally 58

75. LYSOGENIC (TEMPERATE) PHAGES
Upon infection phage inserts its DNA into the host chromosome (prophage)
Prophage genes may alter host cell characteristics by transduction 59

76. Phage picks up, randomly, fragments of host DNA instead of phage’s DNA
TRANSDUCTION
Generalized
Phage picks up, randomly, fragments of host DNA instead of phage’s DNA
May transfer any gene 60

77. TRANSDUCTION (cont.) Specialized
Phage DNA that has been integrated to host DNA is exised along with a few adjacent host genes 61

78. LYSOGENIC PHAGES (cont.)
Toxins produced by:
Corynebacterium diphteriae
Streptococcus pyogenes
Clostridium botulinum 62

79. VIRAL MULTIPLICATION Attachment Penetration Biosynthesis Maturation
Release 63

87. Viral nucleic acid gets integrated into host genome
ONCOGENIC VIRUSES
Viral nucleic acid gets integrated into host genome
Alteration of cellular growth genes 70

88. LATENT VIRAL INFECTIONS
Virus/host equilibrium
Herpes viruses
Cold sores
Shingles (chicken pox) 71

89. Virus builds up gradually Usually fatal
SLOW VIRAL INFECTIONS
Virus builds up gradually
Usually fatal
Subacute sclerosing panencephalitis 72

90. Undetectable nucleic acid?, a bacterium? Neurological diseases
PRIONS
Protein
Undetectable nucleic acid?, a bacterium?
Neurological diseases
Creutzfeldt-Jacob disease
Mad cow disease 73

91. HOST CELL DEFENSES

92. Antiviral proteins (AVP) produced by virus-infected cells
INTERFERON (IFN)
Antiviral proteins (AVP) produced by virus-infected cells
Interfere with viral multiplication 74

94. No effect on infected cells
INTERFERON (cont.)
Host-cell specific
Not virus specific
Short lived
No effect on infected cells 75

95. INTERFERON TYPES
Alpha (a-IFN)
Beta (b-IFN)
Gamma (g-IFN) 76

96. IFNs diffuse and gain entrance to non-infected neighboring cells
INTERFERON ACTIVITY
IFNs diffuse and gain entrance to non-infected neighboring cells
Induce synthesis of antiviral proteins 77

97. Destruction of viral mRNA Inhibit translation of viral mRNA
INTERFERON ACTIVITY
Antiviral proteins:
Destruction of viral mRNA
Inhibit translation of viral mRNA
Inhibit polypeptide elongation 78

98. RABBITS AND MYXOMATOSIS79

99. Introduced Rabbits First arrived in 1778 from Europe
AUSTRALIA
Introduced Rabbits First arrived in 1778 from Europe
Spread 125 Km/year
Soon became a pest 80

100. Mild infection in Australian native rabbits
MYXOMATOSIS
Caused by a poxvirus
Mild infection in Australian native rabbits
Fatal infection in the introduced European rabbits 81

101. TRANSMISSION OF MYXOMATOSIS
Mosquito
Flea
Direct contact 82

102. MYXOMA VIRUS IN AUSTRALIA
Introduced in the Summer
By 1956 the European rabbit population dropped 90% 83

103. MYXOMA VIRUS IN AUSTRALIA (cont.)
As time went on:
Rabbit population began to recover
Appearance of less virulent viruses
Appearance of more resistant rabbits 84