Lecture #1 of the Columbia University Virology Course W3310 by Prof. Vincent Racaniello.

4. Biology W3310
Virology

5. Biology W3310
Virology
• Prof. Vincent Racaniello, Ph.D.

6. Biology W3310
Virology
• Prof. Vincent Racaniello, Ph.D.
- vrr1@columbia.edu

7. Biology W3310
Virology
• Prof. Vincent Racaniello, Ph.D.
- vrr1@columbia.edu
- twitter.com/@profvrr

8. Biology W3310
Virology
• Prof. Vincent Racaniello, Ph.D.
- vrr1@columbia.edu
- twitter.com/@profvrr
• Prof. Saul Silverstein, Ph.D.

9. Biology W3310
Virology
• Prof. Vincent Racaniello, Ph.D.
- vrr1@columbia.edu
- twitter.com/@profvrr
• Prof. Saul Silverstein, Ph.D.
- sjs6@columbia.edu

10. Biology W3310
Virology
• Prof. Vincent Racaniello, Ph.D.
- vrr1@columbia.edu
- twitter.com/@profvrr
• Prof. Saul Silverstein, Ph.D.
- sjs6@columbia.edu
• TA: Esther Francisco

11. Biology W3310
Virology
• Prof. Vincent Racaniello, Ph.D.
- vrr1@columbia.edu
- twitter.com/@profvrr
• Prof. Saul Silverstein, Ph.D.
- sjs6@columbia.edu
• TA: Esther Francisco
- ef197@columbia.edu

12. Biology W3310
Virology

13. Biology W3310
Virology
• Courseworks or
http://microbiology.columbia.edu/
w3310.html

14. Biology W3310
Virology
• Courseworks or
http://microbiology.columbia.edu/
w3310.html
- Schedule, readings, screencasts

15. Biology W3310
Virology
• Courseworks or
http://microbiology.columbia.edu/
w3310.html
- Schedule, readings, screencasts
• Textbook: Principles of Virology,
Third Edition, ASM Press

16. Biology W3310
Virology
• Courseworks or
http://microbiology.columbia.edu/
w3310.html
- Schedule, readings, screencasts
• Textbook: Principles of Virology,
Third Edition, ASM Press
• virology blog: www.virology.ws

17. Biology W3310
Virology
• Courseworks or
http://microbiology.columbia.edu/
w3310.html
- Schedule, readings, screencasts
• Textbook: Principles of Virology,
Third Edition, ASM Press
• virology blog: www.virology.ws
• This Week in Virology: www.twiv.tv

20. All living things survive in a sea of
viruses

21. All living things survive in a sea of
viruses
• We eat and breathe billions of them regularly

22. All living things survive in a sea of
viruses
• We eat and breathe billions of them regularly
-breathe 6 liters of air per minute, eat thousands of grams of
food and its allied contaminants per day, touch heaven knows
what and put our fingers in our eyes and mouths

23. All living things survive in a sea of
viruses
• We eat and breathe billions of them regularly
-breathe 6 liters of air per minute, eat thousands of grams of
food and its allied contaminants per day, touch heaven knows
what and put our fingers in our eyes and mouths
-every milliliter of seawater has more than a million virus
particles

24. All living things survive in a sea of
viruses
• We eat and breathe billions of them regularly
-breathe 6 liters of air per minute, eat thousands of grams of
food and its allied contaminants per day, touch heaven knows
what and put our fingers in our eyes and mouths
-every milliliter of seawater has more than a million virus
particles
• We carry viral genomes as part of our own genetic material

25. All living things survive in a sea of
viruses
• We eat and breathe billions of them regularly
-breathe 6 liters of air per minute, eat thousands of grams of
food and its allied contaminants per day, touch heaven knows
what and put our fingers in our eyes and mouths
-every milliliter of seawater has more than a million virus
particles
• We carry viral genomes as part of our own genetic material
• Viruses infect our pets, domestic food animals, wildlife,
plants, insects

26. All living things survive in a sea of
viruses
• We eat and breathe billions of them regularly
-breathe 6 liters of air per minute, eat thousands of grams of
food and its allied contaminants per day, touch heaven knows
what and put our fingers in our eyes and mouths
-every milliliter of seawater has more than a million virus
particles
• We carry viral genomes as part of our own genetic material
• Viruses infect our pets, domestic food animals, wildlife,
plants, insects
• Viral infections can cross species barriers, and do so
constantly - zoonotic infections

27. All living things survive in a sea of
viruses
• We eat and breathe billions of them regularly
-breathe 6 liters of air per minute, eat thousands of grams of
food and its allied contaminants per day, touch heaven knows
what and put our fingers in our eyes and mouths
-every milliliter of seawater has more than a million virus
particles
• We carry viral genomes as part of our own genetic material
• Viruses infect our pets, domestic food animals, wildlife,
plants, insects
• Viral infections can cross species barriers, and do so
constantly - zoonotic infections

28. The number of viruses impinging on us
is staggering

29. The number of viruses impinging on us
is staggering
More than 1030
bacteriophage particles in the
world’s water supply!

30. The number of viruses impinging on us
is staggering
More than 1030
bacteriophage particles in the
world’s water supply!
• A bacteriophage particle weighs about a
femtogram (10-15 grams)

31. The number of viruses impinging on us
is staggering
More than 1030
bacteriophage particles in the
world’s water supply!
• A bacteriophage particle weighs about a
femtogram (10-15 grams)
1030 X 10-15= the biomass on the planet of
BACTERIAL VIRUSES ALONE exceeds the
biomass of elephants by more than 1000-
fold!

32. The number of viruses impinging on us
is staggering
More than 1030
bacteriophage particles in the
world’s water supply!
• A bacteriophage particle weighs about a
femtogram (10-15 grams)
1030 X 10-15= the biomass on the planet of
BACTERIAL VIRUSES ALONE exceeds the
biomass of elephants by more than 1000-
fold!
•The length of a head to tail line of 1030 phages
is more than 200 million light years!
(calculation: http://www.phagehunter.org/
2008/09/how-far-do-those-phages-
stretch.html)

33. Andromeda Galaxy - 2.5 million light years away

35. •Whales are commonly infected with a tiny virus of the Caliciviridae
family

36. •Whales are commonly infected with a tiny virus of the Caliciviridae
family
•These whale diarrhea viruses cause rashes, blisters, gastroenteritis
in marine mammals

37. •Whales are commonly infected with a tiny virus of the Caliciviridae
family
•These whale diarrhea viruses cause rashes, blisters, gastroenteritis
in marine mammals
•They may infect humans

38. •Whales are commonly infected with a tiny virus of the Caliciviridae
family
•These whale diarrhea viruses cause rashes, blisters, gastroenteritis
in marine mammals
•They may infect humans
•Infected whales secrete more than 1013 calciviruses daily!!

39. There are
~1016 HIV genomes
on the planet today

40. There are ~10
HIV genomes
16
on the planet today
With this number of genomes, it is highly
probable that
HIV genomes exist that are resistant to every
one of the antiviral drugs that we have now,

41. Amazingly, the vast majority of
the viruses that infect us have
little or no impact on our health

42. Amazingly, the vast majority of
the viruses that infect us have
little or no impact on our health
We exist because we have a defense system
that evolved to fight infections

43. Amazingly, the vast majority of
the viruses that infect us have
little or no impact on our health
We exist because we have a defense system
that evolved to fight infections

44. Amazingly, the vast majority of
the viruses that infect us have
little or no impact on our health
We exist because we have a defense system
that evolved to fight infections
If our immune system is down (e.g. AIDS,
organ transplants), even the most common
viral infection can be lethal

45. How ‘infected’ are we?

46. How ‘infected’ are we?
•Each of you in this room is probably infected
with at least 2 of the 9 known herpesviruses:

47. How ‘infected’ are we?
•Each of you in this room is probably infected
with at least 2 of the 9 known herpesviruses:
•HSV-1, HSV-2, VZV, HCMV, EBV, HHV-6,
HHV-7, HHV-8, B virus (the latter is 100%
lethal for humans, so you probably haven’t
seen this one)

48. How ‘infected’ are we?
•Each of you in this room is probably infected
with at least 2 of the 9 known herpesviruses:
•HSV-1, HSV-2, VZV, HCMV, EBV, HHV-6,
HHV-7, HHV-8, B virus (the latter is 100%
lethal for humans, so you probably haven’t
seen this one)
•Once infected with any of these (except B

49. Every one of your cells is
infected with viruses

50. Every one of your cells is
infected with viruses
•Each of you has thousands of copies of old
and new retrovirus genomes integrated into
your DNA

51. Every one of your cells is
infected with viruses
•Each of you has thousands of copies of old
and new retrovirus genomes integrated into
your DNA
•About 8% of your DNA is made up of these
ancient genomes

52. Every one of your cells is
infected with viruses
•Each of you has thousands of copies of old
and new retrovirus genomes integrated into
your DNA
•About 8% of your DNA is made up of these
ancient genomes
•You will pass these novel entities on to your
children and they will do the same to their
offspring

53. Every one of your cells is
infected with viruses
•Each of you has thousands of copies of old
and new retrovirus genomes integrated into
your DNA
•About 8% of your DNA is made up of these
ancient genomes
•You will pass these novel entities on to your
children and they will do the same to their
offspring
•What are these genomes doing there?

54. You are a reservoir for viruses
that have set up residence in
your lungs and gastrointestinal
tract (plus a few other places)

55. You are a reservoir for viruses
that have set up residence in
your lungs and gastrointestinal
tract (plus a few other places)
•All of us are colonized by a variety of
adenoviruses, coronaviruses, and rhinoviruses

56. You are a reservoir for viruses
that have set up residence in
your lungs and gastrointestinal
tract (plus a few other places)
•All of us are colonized by a variety of
adenoviruses, coronaviruses, and rhinoviruses
•Our guts are loaded with bacteria harboring
their own blend of viruses

57. You are a reservoir for viruses
that have set up residence in
your lungs and gastrointestinal
tract (plus a few other places)
•All of us are colonized by a variety of
adenoviruses, coronaviruses, and rhinoviruses
•Our guts are loaded with bacteria harboring
their own blend of viruses
•Viruses have been with humans since the
beginning of our existence

58. Viruses are amazing
This course will teach you why

60. •This course is designed to help you see the
‘big picture’ of virology

61. •This course is designed to help you see the
‘big picture’ of virology
•I’ll show you how to think about virology as
an integrative discipline, not an isolated
collection of viruses, diseases, or genes

62. •This course is designed to help you see the
‘big picture’ of virology
•I’ll show you how to think about virology as
an integrative discipline, not an isolated
collection of viruses, diseases, or genes
•I want you to appreciate the molecular
wizardry practiced by an often unpredictable
organism that pervades the entire ecosystem

63. •This course is designed to help you see the
‘big picture’ of virology
•I’ll show you how to think about virology as
an integrative discipline, not an isolated
collection of viruses, diseases, or genes
•I want you to appreciate the molecular
wizardry practiced by an often unpredictable
organism that pervades the entire ecosystem
•I want you to learn the fundamentals about
these molecular wizards that continue to
amaze the informed and frighten those who
don’t understand the first principles

65. •Virology requires that you know a little
about almost every subject in biology

66. •Virology requires that you know a little
about almost every subject in biology
•Virology constantly tests your ability to think
and pull information together

67. •Virology requires that you know a little
about almost every subject in biology
•Virology constantly tests your ability to think
and pull information together
•While you must memorize the facts, you
cannot memorize the many combinations of
facts that define viruses. You have to think.

68. •Virology requires that you know a little
about almost every subject in biology
•Virology constantly tests your ability to think
and pull information together
•While you must memorize the facts, you
cannot memorize the many combinations of
facts that define viruses. You have to think.
•The devil and the delight are in the details of
learning the strategies and tactics of viruses

69. One of the reasons kids get bored by science is that
too many teachers present it as a fusty* collection of
facts for memorization. This is precisely wrong.
Science isn’t about facts. It’s about the quest for facts
— the scientific method, the process by which we
hash through confusing thickets of ignorance. It’s
dynamic, argumentative, collaborative, competitive,
filled with flashes of crazy excitement and hours of
drudgework, and driven by ego: Our desire to be the
one who figures it out, at least for now.
Clive Thompson, Wired 09.08.08

71. •Viruses are a significant part of the
ecosystem, infecting every living thing

72. •Viruses are a significant part of the
ecosystem, infecting every living thing
•Yet, to the uninitiated, viruses are ‘bad news
wrapped in a bit of protein’

73. •Viruses are a significant part of the
ecosystem, infecting every living thing
•Yet, to the uninitiated, viruses are ‘bad news
wrapped in a bit of protein’
•Believe me - viruses do much more than
cause disease

74. The Big Picture: A common strategy,
unity in diversity

75. The Big Picture: A common strategy,
unity in diversity
The basic thesis of this course is that ALL viruses
follow a simple three part general strategy to ensure
survival:

76. The Big Picture: A common strategy,
unity in diversity
The basic thesis of this course is that ALL viruses
follow a simple three part general strategy to ensure
survival:
1. All viruses package their genomes inside a particle
used for transmission of the genome from host to
host

77. The Big Picture: A common strategy,
unity in diversity
The basic thesis of this course is that ALL viruses
follow a simple three part general strategy to ensure
survival:
1. All viruses package their genomes inside a particle
used for transmission of the genome from host to
host
2. The viral genome contains the information to initiate
and complete an infectious cycle within a susceptible
and permissive cell

78. The Big Picture: A common strategy,
unity in diversity
The basic thesis of this course is that ALL viruses
follow a simple three part general strategy to ensure
survival:
1. All viruses package their genomes inside a particle
used for transmission of the genome from host to
host
2. The viral genome contains the information to initiate
and complete an infectious cycle within a susceptible
and permissive cell
3. All viral genomes are able to establish themselves in a
host population so that viral survival is ensured

79. Why study virology if this is all there is
to it?

80. Why study virology if this is all there is
to it?
• Despite this simple 3-part strategy, the tactics used
to achieve it are incredibly diverse

81. Why study virology if this is all there is
to it?
• Despite this simple 3-part strategy, the tactics used
to achieve it are incredibly diverse
• There are countless virus particles out there with
amazing diversity:

82. Why study virology if this is all there is
to it?
• Despite this simple 3-part strategy, the tactics used
to achieve it are incredibly diverse
• There are countless virus particles out there with
amazing diversity:
- size, nature and topology of genomes

83. Why study virology if this is all there is
to it?
• Despite this simple 3-part strategy, the tactics used
to achieve it are incredibly diverse
• There are countless virus particles out there with
amazing diversity:
- size, nature and topology of genomes
- strange particles

84. Why study virology if this is all there is
to it?
• Despite this simple 3-part strategy, the tactics used
to achieve it are incredibly diverse
• There are countless virus particles out there with
amazing diversity:
- size, nature and topology of genomes
- strange particles
- unbelievable coding strategies

85. Why study virology if this is all there is
to it?
• Despite this simple 3-part strategy, the tactics used
to achieve it are incredibly diverse
• There are countless virus particles out there with
amazing diversity:
- size, nature and topology of genomes
- strange particles
- unbelievable coding strategies
- amazing tissue/cell tropism

86. Why study virology if this is all there is
to it?
• Despite this simple 3-part strategy, the tactics used
to achieve it are incredibly diverse
• There are countless virus particles out there with
amazing diversity:
- size, nature and topology of genomes
- strange particles
- unbelievable coding strategies
- amazing tissue/cell tropism
- degrees of pathogenesis from benign to lethal

87. Nevertheless, there is an
underlying simplicity and order
to viruses because of two simple

88. Nevertheless, there is an
underlying simplicity and order
to viruses because of two simple
• All viral genomes are obligate
molecular parasites that can only
function after they replicate in a cell

89. Nevertheless, there is an
underlying simplicity and order
to viruses because of two simple
• All viral genomes are obligate
molecular parasites that can only
function after they replicate in a cell
• All viruses must make mRNA that
can be translated by host
ribosomes: they are all parasites of
the host protein synthesis
machinery

90. As viruses are obligate molecular parasites, every
solution must reveal something about the host as
well as the virus

91. Be careful: Avoid anthropomorphic
analyses

92. Be careful: Avoid anthropomorphic
analyses
Viruses do NOT think!

93. Be careful: Avoid anthropomorphic
analyses
Viruses do NOT think!
(or employ, ensure, exhibit, display, etc...)

94. Be careful: Avoid anthropomorphic
analyses
Viruses do NOT think!
(or employ, ensure, exhibit, display, etc...)
They do not achieve their goals in a human-centered
manner

95. Be careful: Avoid anthropomorphic
analyses
Viruses do NOT think!
(or employ, ensure, exhibit, display, etc...)
They do not achieve their goals in a human-centered
manner

96. Be careful: Avoid anthropomorphic
analyses
Viruses do NOT think!
(or employ, ensure, exhibit, display, etc...)
They do not achieve their goals in a human-centered
manner
They survive because they make huge numbers of
mutants, and selection removes the ill-adapted

97. Viruses are simple ‘Darwinian Machines’

98. Viruses are simple ‘Darwinian Machines’
• There is no better model for the concept of ‘survival
of the fittest’

99. Viruses are simple ‘Darwinian Machines’
• There is no better model for the concept of ‘survival
of the fittest’
• Think about this a bit more....viruses depend upon
their hosts to survive

100. Viruses are simple ‘Darwinian Machines’
• There is no better model for the concept of ‘survival
of the fittest’
• Think about this a bit more....viruses depend upon
their hosts to survive
• If viruses are too successful and kill their hosts,
they may eliminate themselves

101. Viruses are simple ‘Darwinian Machines’
• There is no better model for the concept of ‘survival
of the fittest’
• Think about this a bit more....viruses depend upon
their hosts to survive
• If viruses are too successful and kill their hosts,
they may eliminate themselves
• If they are too passive and their hosts’ defenses
impede their growth, they may be eliminated

103. How is the balance of host and virus survival
established?

104. How is the balance of host and virus survival
established?
The often unexpected twists and turns that lead to
virus survival in cells, tissues, organisms, and in a
population provide insight into biology and molecular
mechanisms not otherwise possible

105. After this course is over, you will have:

106. After this course is over, you will have:
• Significantly better insight into how cells work and
interact

107. After this course is over, you will have:
• Significantly better insight into how cells work and
interact
- viruses are a biological ‘wedge’ or ‘hook’ to target
complex processes

108. After this course is over, you will have:
• Significantly better insight into how cells work and
interact
- viruses are a biological ‘wedge’ or ‘hook’ to target
complex processes
• A glimpse of the many ways that information is
stored and decoded in genomes

109. After this course is over, you will have:
• Significantly better insight into how cells work and
interact
- viruses are a biological ‘wedge’ or ‘hook’ to target
complex processes
• A glimpse of the many ways that information is
stored and decoded in genomes
- how such powerful information can be packed and
retrieved from such small viral genomes

110. After this course is over, you will have:
• Significantly better insight into how cells work and
interact
- viruses are a biological ‘wedge’ or ‘hook’ to target
complex processes
• A glimpse of the many ways that information is
stored and decoded in genomes
- how such powerful information can be packed and
retrieved from such small viral genomes
• A basic understanding of viral pathogenesis and
infectious disease in general

111. After this course is over, you will have:
• Significantly better insight into how cells work and
interact
- viruses are a biological ‘wedge’ or ‘hook’ to target
complex processes
• A glimpse of the many ways that information is
stored and decoded in genomes
- how such powerful information can be packed and
retrieved from such small viral genomes
• A basic understanding of viral pathogenesis and
infectious disease in general
- why do you feel so badly when some viruses have
their way with you? Immunology actually makes
sense when you understand viruses

112. Assertions you should be able to defend
when the course is over

113. Assertions you should be able to defend
when the course is over
• Viruses have more biological diversity than all the
rest of the bacterial, plant, and animal kingdoms put
together

114. Assertions you should be able to defend
when the course is over
• Viruses have more biological diversity than all the
rest of the bacterial, plant, and animal kingdoms put
together
• Humans are not at the top of the food chain; the
tiny may well inherit the earth

115. Assertions you should be able to defend
when the course is over
• Viruses have more biological diversity than all the
rest of the bacterial, plant, and animal kingdoms put
together
• Humans are not at the top of the food chain; the
tiny may well inherit the earth
• Despite their diminutive size (most viruses have less
than 15 genes, some have only 1), viruses excel at
survival in a harsh world using sophisticated
molecular biology

116. Assertions you should be able to defend
when the course is over
• Viruses have more biological diversity than all the
rest of the bacterial, plant, and animal kingdoms put
together
• Humans are not at the top of the food chain; the
tiny may well inherit the earth
• Despite their diminutive size (most viruses have less
than 15 genes, some have only 1), viruses excel at
survival in a harsh world using sophisticated
molecular biology
• Virus-host interactions define molecular interactions
of fundamental and practical significance that must
be understood if we are to defend ourselves against
viruses

119. • This course will emphasize animal
viruses, with some discussion of
bacterial viruses

120. • This course will emphasize animal
viruses, with some discussion of
bacterial viruses
• Many viruses will be ignored simply
because of time constraints

121. How old are viruses?

122. How old are viruses?
• With few exceptions there is no fossil
record

123. How old are viruses?
• With few exceptions there is no fossil
record
• Estimates of molecular evolution place
some viruses among the dinosaurs

124. How old are viruses?
• With few exceptions there is no fossil
record
• Estimates of molecular evolution place
some viruses among the dinosaurs
• In theory viruses could pre-date
cellular life

125. Ancient references to viral
700 B.C.
1580-1350 B.C.

127. • Prevention of virus infections in
practice since the 11th century
without knowledge of agent

128. • Prevention of virus infections in
practice since the 11th century
without knowledge of agent
• Based on recognition that survivors
of smallpox were subsequently
protected against disease

129. • Prevention of virus infections in
practice since the 11th century
without knowledge of agent
• Based on recognition that survivors
of smallpox were subsequently
protected against disease
• Variolation - inoculation of healthy
individuals with material from a
smallpox pustule (Lady Montagu)

130. • Prevention of virus infections in
practice since the 11th century
without knowledge of agent
• Based on recognition that survivors
of smallpox were subsequently
protected against disease
• Variolation - inoculation of healthy
individuals with material from a
smallpox pustule (Lady Montagu)
• 1790s - experiments by Edward
Jenner in England establish

131. Concept of microorganisms

132. Concept of microorganisms
• Leeuwenhoek (1632 - 1723) made
microscopes, discovered “wee
animalcules”, lead to acceptance of
microorganisms

133. Concept of microorganisms
• Leeuwenhoek (1632 - 1723) made
microscopes, discovered “wee
animalcules”, lead to acceptance of
microorganisms
• Pasteur (1822 - 1895) showed that
microorganisms were generated by
reproduction, not spontaneous
generation

134. Concept of microorganisms
• Leeuwenhoek (1632 - 1723) made
microscopes, discovered “wee
animalcules”, lead to acceptance of
microorganisms
• Pasteur (1822 - 1895) showed that
microorganisms were generated by
reproduction, not spontaneous
generation
• The Germ Theory of disease,
formally enunciated by Koch in

135. Pasteur’s swan-neck flask
http://www.twiv.tv/2009/06/07/twiv-35-much-achoo-about-nothing/

137. Virus discovery - filterable
agents

138. Virus discovery - filterable
agents
• 1892 - Ivanovsky -
found the agent of
tobacco mosaic
disease passes
through filters that
retain bacteria

139. Virus discovery - filterable
agents
• 1892 - Ivanovsky -
found the agent of
tobacco mosaic
disease passes
through filters that
retain bacteria
• 1898 - Beijerinck
made same finding,
but suggested that
the pathogen is a
distinct agent, not

140. Virus discovery

141. Virus discovery
• 1898 - Loeffler & Frosch - agent of
foot & mouth disease is filterable

142. Virus discovery
• 1898 - Loeffler & Frosch - agent of
foot & mouth disease is filterable
• Key concept: agents not only small,
but replicate only in the host, not in
broth

143. Virus discovery
• 1898 - Loeffler & Frosch - agent of
foot & mouth disease is filterable
• Key concept: agents not only small,
but replicate only in the host, not in
broth
• 0.2 micron filters (µm, one millionth
of a meter)

144. Virus discovery
• 1901 - first human virus, yellow
fever virus
• 1903 - rabies virus
• 1906 - variola virus
• 1908 - chicken leukemia virus,
poliovirus
• 1911 - Rous sarcoma virus
• 1915 - bacteriophages
• 1933 - influenza virus

145. Virus
From the Latin meaning toxin or poison

146. Virus
From the Latin meaning toxin or poison
virion = infectious particle

148. We know many details about
Chemical formula for
poliovirus: C332,652 H492,388
N98,245 O131,196 P7,501 S2,340

149. What is a virus?

150. What is a virus?
• A virus is a very small, infectious, obligate
intracellular parasite

151. What is a virus?
• A virus is a very small, infectious, obligate
intracellular parasite
• Parasite: organism benefits at the expense
of the host (a different organism)

152. What is a virus?
• A virus is a very small, infectious, obligate
intracellular parasite
• Parasite: organism benefits at the expense
of the host (a different organism)
• Virus particles are not living

153. What is a virus?
• A virus is a very small, infectious, obligate
intracellular parasite
• Parasite: organism benefits at the expense
of the host (a different organism)
• Virus particles are not living
• Viruses are chemicals, and by themselves
cannot reproduce

154. What is a virus?
• A virus is a very small, infectious, obligate
intracellular parasite
• Parasite: organism benefits at the expense
of the host (a different organism)
• Virus particles are not living
• Viruses are chemicals, and by themselves
cannot reproduce
• A cellular host is needed for viruses to

155. Are viruses alive?
http://www.virology.ws/2009/11/23/are-viruses-alive/

156. Viruses are very
small Carbon atom
ribosome
HIV-1
phage
TMV
poliovirus
myosin actin
1,000,000x
E. coli 100,000x

158. How many viruses can fit on the
head of a pin?
• 500 million rhinoviruses - one of
the causes of the common cold
• When you sneeze, you fire an
aerosol that contains enough
viruses to infect thousands

159. Very small?

160. Very small?
• Mimivirus: largest known virus

161. Very small?
• Mimivirus: largest known virus
• host: Amoebae

162. Very small?
• Mimivirus: largest known virus
• host: Amoebae
• 500 nm particle + 125 nm fibers = 750 nm or
0.75 μm

163. Very small?
• Mimivirus: largest known virus
• host: Amoebae
• 500 nm particle + 125 nm fibers = 750 nm or
0.75 μm
• 1,181,404 bp ds DNA genome encodes 1262 open
reading frames

164. Very small?
• Mimivirus: largest known virus
• host: Amoebae
• 500 nm particle + 125 nm fibers = 750 nm or
0.75 μm
• 1,181,404 bp ds DNA genome encodes 1262 open
reading frames
• Encodes four amino-acyl tRNA synthetases,
peptide release factor 1, translation elongation
factor EF-TU, translation initiation factor 1, six
tRNAs, both type I and type II topoisomerases,
components of all DNA repair pathways, many
polysaccharide synthesis enzymes

165. Mimivirus particles can be seen by
light microscopy
giantvirus.or
g

166. Defining viral attributes

167. Defining viral attributes
• The genome is comprised of either DNA or RNA

168. Defining viral attributes
• The genome is comprised of either DNA or RNA
• Within an appropriate host cell, the viral genome
directs the synthesis, by cellular systems, of the
components needed for replication of the viral
genome and its transmission within virus particles

169. Defining viral attributes
• The genome is comprised of either DNA or RNA
• Within an appropriate host cell, the viral genome
directs the synthesis, by cellular systems, of the
components needed for replication of the viral
genome and its transmission within virus particles
• New virus particles are formed by de novo assembly
from newly-synthesized components within the host
cell

170. Defining viral attributes
• The genome is comprised of either DNA or RNA
• Within an appropriate host cell, the viral genome
directs the synthesis, by cellular systems, of the
components needed for replication of the viral
genome and its transmission within virus particles
• New virus particles are formed by de novo assembly
from newly-synthesized components within the host
cell
• The progeny particles are the vehicles for
transmission of the viral genome to the next host
cell or organism

171. Defining viral attributes
• The genome is comprised of either DNA or RNA
• Within an appropriate host cell, the viral genome
directs the synthesis, by cellular systems, of the
components needed for replication of the viral
genome and its transmission within virus particles
• New virus particles are formed by de novo assembly
from newly-synthesized components within the host
cell
• The progeny particles are the vehicles for
transmission of the viral genome to the next host
cell or organism
• The particles are then disassembled inside the new
cell, initiating the next infectious cycle

172. A viral infection is an exercise in cell
biology
Many cell functions
required for viral
propagation
– machinery for
translation of viral
mRNAs
– Energy
– enzymes for replication
and assembly
– transport pathways

173. Viruses replicate by
assembly of pre-
formed
components into
many particles
First make the parts,
then assemble the
final product.
Not binary fission like
cells

174. Virus classification
• Classical hierarchical system:
Kingdom
Phylum
Class
Order
Family
Genus
Species

175. Virus classification

176. Virus classification
• Viruses are classified according to
four main characteristics:

177. Virus classification
• Viruses are classified according to
four main characteristics:
- nature of nucleic acid in virion

178. Virus classification
• Viruses are classified according to
four main characteristics:
- nature of nucleic acid in virion
- symmetry of protein shell (capsid)

179. Virus classification
• Viruses are classified according to
four main characteristics:
- nature of nucleic acid in virion
- symmetry of protein shell (capsid)
- presence or absence of lipid
membrane (envelope)

180. Virus classification
• Viruses are classified according to
four main characteristics:
- nature of nucleic acid in virion
- symmetry of protein shell (capsid)
- presence or absence of lipid
membrane (envelope)
- dimensions of virion & capsid

181. Virus classification
• Viruses are classified according to
four main characteristics:
- nature of nucleic acid in virion
- symmetry of protein shell (capsid)
- presence or absence of lipid
membrane (envelope)
- dimensions of virion & capsid
• Genomics has also become

183. Family: Picornaviridae (picornavirus
from ViralZone
http://www.expasy.ch/viralzone/

184. http://

185. • 40,000 virus isolates from bacteria,
plants, animals placed in 3 orders,
73 families, 287 genera, 1950
species.
• BUT - there are 106 virions per ml
of seawater - most of them
unknown!

186. Viral Genomes
BREAKTHROUGH in the 1950s:
The viral nucleic acid genome was shown to
carry the information needed to replicate, build,
and spread virions in the world; it IS the genetic
code
- seems obvious now, but this discovery in
viruses was one of the building blocks of
Molecular Biology

187. Alfred Hershey & Margaret Chase, 1952

188. Key fact makes life easier for
students of virology:
Viral genomes must make mRNA
that can be read by host ribosomes
- all viruses on the planet follow this rule, no
exception to date

189. Key fact makes life easier for
students of virology:
Viral genomes must make mRNA
that can be read by host ribosomes
- all viruses on the planet follow this rule, no
exception to date
Although there are thousands of different virions, there is only
a finite number of viral genomes: There are only SEVEN genome
types

190. David Baltimore (Nobel laureate) used this
insight to describe a simple way to think
about virus genomes
- a major unifying principle in virology

191. David Baltimore (Nobel laureate) used this
insight to describe a simple way to think
about virus genomes
- a major unifying principle in virology
The original Baltimore system missed
one genome type: the gapped DNA of
the Hepadnaviridae

192. Definitions
• (+) strand: mRNA, because it can be
immediately translated. A strand of
DNA of the equivalent polarity is
also (+) strand
• (-) strand: the complement of the
(+) strand; cannot be translated

193. The elegance of the Baltimore system
Knowing only the nature of the viral genome,
one can deduce the basic steps that must
take place
to produce mRNA

194. The seven classes of viral
genomes
• dsRNA
• dsDNA
• ss (+) RNA
• gapped dsDNA
• ss (-) RNA
• ssDNA
• ss (+) RNA with DNA
intermediate