Biology W3310
   Virology
Biology W3310
            Virology

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

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

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

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

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

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

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

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

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

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

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

• Courseworks or
  http://microbiology.columbia.edu/
  w3310.html
 - Schedule, reading...
All living things survive in a sea of
viruses
All living things survive in a sea of
    viruses
• We eat and breathe billions of them regularly
All living things survive in a sea of
    viruses
• We eat and breathe billions of them regularly
  -breathe 6 liters of a...
All living things survive in a sea of
    viruses
• We eat and breathe billions of them regularly
  -breathe 6 liters of a...
All living things survive in a sea of
    viruses
• We eat and breathe billions of them regularly
  -breathe 6 liters of a...
All living things survive in a sea of
    viruses
• We eat and breathe billions of them regularly
  -breathe 6 liters of a...
All living things survive in a sea of
    viruses
• We eat and breathe billions of them regularly
  -breathe 6 liters of a...
All living things survive in a sea of
    viruses
• We eat and breathe billions of them regularly
  -breathe 6 liters of a...
The number of viruses impinging on us
           is staggering
The number of viruses impinging on us
           is staggering
                     More than 1030
              bacteriop...
The number of viruses impinging on us
           is staggering
                     More than 1030
              bacteriop...
The number of viruses impinging on us
           is staggering
                     More than 1030
              bacteriop...
The number of viruses impinging on us
           is staggering
                     More than 1030
              bacteriop...
Andromeda Galaxy - 2.5 million light years away
•Whales are commonly infected with a tiny virus of the Caliciviridae
family
•Whales are commonly infected with a tiny virus of the Caliciviridae
family

•These whale diarrhea viruses cause rashes, b...
•Whales are commonly infected with a tiny virus of the Caliciviridae
family

•These whale diarrhea viruses cause rashes, b...
•Whales are commonly infected with a tiny virus of the Caliciviridae
family

•These whale diarrhea viruses cause rashes, b...
There are
        ~1016  HIV genomes
    on the planet today
There are     ~10
               HIV genomes
                 16

    on the planet today


  With this number of genomes,...
Amazingly, the vast majority of
 the viruses that infect us have
little or no impact on our health
Amazingly, the vast majority of
 the viruses that infect us have
little or no impact on our health



We exist because we ...
Amazingly, the vast majority of
 the viruses that infect us have
little or no impact on our health



We exist because we ...
Amazingly, the vast majority of
 the viruses that infect us have
little or no impact on our health



We exist because we ...
How ‘infected’ are we?
How ‘infected’ are we?

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

•Each of you in this room is probably infected
with at least 2 of the 9 known herpesviruses:

•HSV...
How ‘infected’ are we?

•Each of you in this room is probably infected
with at least 2 of the 9 known herpesviruses:

•HSV...
Every one of your cells is
  infected with viruses
Every one of your cells is
       infected with viruses
•Each of you has thousands of copies of old
and new retrovirus gen...
Every one of your cells is
       infected with viruses
•Each of you has thousands of copies of old
and new retrovirus gen...
Every one of your cells is
       infected with viruses
•Each of you has thousands of copies of old
and new retrovirus gen...
Every one of your cells is
       infected with viruses
•Each of you has thousands of copies of old
and new retrovirus gen...
You are a reservoir for viruses
  that have set up residence in
your lungs and gastrointestinal
 tract (plus a few other p...
You are a reservoir for viruses
   that have set up residence in
 your lungs and gastrointestinal
  tract (plus a few othe...
You are a reservoir for viruses
   that have set up residence in
 your lungs and gastrointestinal
  tract (plus a few othe...
You are a reservoir for viruses
   that have set up residence in
 your lungs and gastrointestinal
  tract (plus a few othe...
Viruses are amazing

This course will teach you why
•This course is designed to help you see the
‘big picture’ of virology
•This course is designed to help you see the
‘big picture’ of virology

•I’ll show you how to think about virology as
an i...
•This course is designed to help you see the
‘big picture’ of virology

•I’ll show you how to think about virology as
an i...
•This course is designed to help you see the
‘big picture’ of virology

•I’ll show you how to think about virology as
an i...
•Virology requires that you know a little
about almost every subject in biology
•Virology requires that you know a little
about almost every subject in biology

•Virology constantly tests your ability t...
•Virology requires that you know a little
about almost every subject in biology

•Virology constantly tests your ability t...
•Virology requires that you know a little
about almost every subject in biology

•Virology constantly tests your ability t...
One of the reasons kids get bored by science is that
too many teachers present it as a fusty* collection of
facts for memo...
•Viruses are a significant part of the
ecosystem, infecting every living thing
•Viruses are a significant part of the
ecosystem, infecting every living thing

•Yet, to the uninitiated, viruses are ‘bad ...
•Viruses are a significant part of the
ecosystem, infecting every living thing

•Yet, to the uninitiated, viruses are ‘bad ...
The Big Picture: A common strategy,
         unity in diversity
The Big Picture: A common strategy,
         unity in diversity
The basic thesis of this course is that ALL viruses
follow...
The Big Picture: A common strategy,
           unity in diversity
  The basic thesis of this course is that ALL viruses
  ...
The Big Picture: A common strategy,
           unity in diversity
  The basic thesis of this course is that ALL viruses
  ...
The Big Picture: A common strategy,
           unity in diversity
  The basic thesis of this course is that ALL viruses
  ...
Why study virology if this is all there is
                to it?
Why study virology if this is all there is
                to it?
•   Despite this simple 3-part strategy, the tactics use...
Why study virology if this is all there is
                to it?
•   Despite this simple 3-part strategy, the tactics use...
Why study virology if this is all there is
                to it?
•   Despite this simple 3-part strategy, the tactics use...
Why study virology if this is all there is
                to it?
•   Despite this simple 3-part strategy, the tactics use...
Why study virology if this is all there is
                to it?
•   Despite this simple 3-part strategy, the tactics use...
Why study virology if this is all there is
                to it?
•   Despite this simple 3-part strategy, the tactics use...
Why study virology if this is all there is
                to it?
•   Despite this simple 3-part strategy, the tactics use...
Nevertheless, there is an
 underlying simplicity and order
to viruses because of two simple
Nevertheless, there is an
 underlying simplicity and order
to viruses because of two simple

• All viral genomes are oblig...
Nevertheless, there is an
 underlying simplicity and order
to viruses because of two simple

• All viral genomes are oblig...
As viruses are obligate molecular parasites, every
solution must reveal something about the host as
well as the virus
Be careful: Avoid anthropomorphic
              analyses
Be careful: Avoid anthropomorphic
               analyses


Viruses do NOT think!
Be careful: Avoid anthropomorphic
               analyses


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


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


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


Viruses do NOT think!
(or employ, ensure, exhibit, display, et...
Viruses are simple ‘Darwinian Machines’
Viruses are simple ‘Darwinian Machines’


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


•   There is no better model for the concept of ‘survival
    of the fittest’

• ...
Viruses are simple ‘Darwinian Machines’


•   There is no better model for the concept of ‘survival
    of the fittest’

• ...
Viruses are simple ‘Darwinian Machines’


•   There is no better model for the concept of ‘survival
    of the fittest’

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


The often unexpected twists and turns that lead to
virus surv...
After this course is over, you will have:
After this course is over, you will have:
•   Significantly better insight into how cells work and
    interact
After this course is over, you will have:
•   Significantly better insight into how cells work and
    interact
    -   vir...
After this course is over, you will have:
•   Significantly better insight into how cells work and
    interact
    -   vir...
After this course is over, you will have:
•   Significantly better insight into how cells work and
    interact
    -   vir...
After this course is over, you will have:
•   Significantly better insight into how cells work and
    interact
    -   vir...
After this course is over, you will have:
•   Significantly better insight into how cells work and
    interact
    -   vir...
Assertions you should be able to defend
        when the course is over
Assertions you should be able to defend
        when the course is over
 •   Viruses have more biological diversity than a...
Assertions you should be able to defend
        when the course is over
 •   Viruses have more biological diversity than a...
Assertions you should be able to defend
        when the course is over
 •   Viruses have more biological diversity than a...
Assertions you should be able to defend
        when the course is over
 •   Viruses have more biological diversity than a...
• This course will emphasize animal
  viruses, with some discussion of
  bacterial viruses
• This course will emphasize animal
  viruses, with some discussion of
  bacterial viruses
• Many viruses will be ignored ...
How old are viruses?
How old are viruses?



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



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



• With few exceptions there is no fossil
  record
• Estimates of molecular evolution place
  some ...
Ancient references to viral




700 B.C.
                   1580-1350 B.C.
• Prevention of virus infections in
  practice since the 11th century
  without knowledge of agent
• Prevention of virus infections in
  practice since the 11th century
  without knowledge of agent
• Based on recognition ...
• Prevention of virus infections in
  practice since the 11th century
  without knowledge of agent
• Based on recognition ...
• Prevention of virus infections in
  practice since the 11th century
  without knowledge of agent
• Based on recognition ...
Concept of microorganisms
Concept of microorganisms

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

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

• Leeuwenhoek (1632 - 1723) made
  microscopes, discovered “wee
  animalcules”, lead to accepta...
Pasteur’s swan-neck flask




http://www.twiv.tv/2009/06/07/twiv-35-much-achoo-about-nothing/
Virus discovery - filterable
          agents
Virus discovery - filterable
            agents
• 1892 - Ivanovsky -
  found the agent of
  tobacco mosaic
  disease passes...
Virus discovery - filterable
            agents
• 1892 - Ivanovsky -
  found the agent of
  tobacco mosaic
  disease passes...
Virus discovery
Virus discovery



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



• 1898 - Loeffler & Frosch - agent of
  foot & mouth disease is filterable
• Key concept: agents not onl...
Virus discovery



• 1898 - Loeffler & Frosch - agent of
  foot & mouth disease is filterable
• Key concept: agents not onl...
Virus discovery

• 1901 - first human virus, yellow
  fever virus
• 1903 - rabies virus
• 1906 - variola virus
• 1908 - chi...
Virus




From the Latin meaning toxin or poison
Virus




From the Latin meaning toxin or poison

virion = infectious particle
We know many details about




Chemical formula for
poliovirus: C332,652 H492,388
N98,245 O131,196 P7,501 S2,340
What is a virus?
What is a virus?

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

• A virus is a very small, infectious, obligate
  intracellular parasite
• Parasite: organism benefits at...
What is a virus?

• A virus is a very small, infectious, obligate
  intracellular parasite
• Parasite: organism benefits at...
What is a virus?

• A virus is a very small, infectious, obligate
  intracellular parasite
• Parasite: organism benefits at...
What is a virus?

• A virus is a very small, infectious, obligate
  intracellular parasite
• Parasite: organism benefits at...
Are viruses alive?




http://www.virology.ws/2009/11/23/are-viruses-alive/
Viruses are very
     small Carbon atom



                   ribosome
HIV-1
              phage
TMV
                   po...
How many viruses can fit on the
       head of a pin?



• 500 million rhinoviruses - one of
  the causes of the common col...
Very small?
Very small?
•   Mimivirus: largest known virus
Very small?
•   Mimivirus: largest known virus
•   host: Amoebae
Very small?
•   Mimivirus: largest known virus
•   host: Amoebae
•   500 nm particle + 125 nm fibers = 750 nm or
    0.75 μm
Very small?
•   Mimivirus: largest known virus
•   host: Amoebae
•   500 nm particle + 125 nm fibers = 750 nm or
    0.75 μ...
Very small?
•   Mimivirus: largest known virus
•   host: Amoebae
•   500 nm particle + 125 nm fibers = 750 nm or
    0.75 μ...
Mimivirus particles can be seen by
           light microscopy




giantvirus.or
      g
Defining viral attributes
Defining viral attributes
•   The genome is comprised of either DNA or RNA
Defining viral attributes
•   The genome is comprised of either DNA or RNA
•   Within an appropriate host cell, the viral g...
Defining viral attributes
•   The genome is comprised of either DNA or RNA
•   Within an appropriate host cell, the viral g...
Defining viral attributes
•   The genome is comprised of either DNA or RNA
•   Within an appropriate host cell, the viral g...
Defining viral attributes
•   The genome is comprised of either DNA or RNA
•   Within an appropriate host cell, the viral g...
A viral infection is an exercise in cell
                   biology
Many cell functions
 required for viral
 propagation
 ...
Viruses replicate by
 assembly of pre-
      formed
 components into
   many particles

 First make the parts,
  then asse...
Virus classification

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

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

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

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

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

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

• Viruses are classified according to
  four main characteristics:
 - nature of nucleic acid in virion...
Family: Picornaviridae (picornavirus




                  from ViralZone
         http://www.expasy.ch/viralzone/
http://
• 40,000 virus isolates from bacteria,
    plants, animals placed in 3 orders,
    73 families, 287 genera, 1950
    speci...
Viral Genomes


BREAKTHROUGH in the 1950s:

The viral nucleic acid genome was shown to
carry the information needed to rep...
Alfred Hershey & Margaret Chase, 1952
Key fact makes life easier for
     students of virology:

     Viral genomes must make mRNA
    that can be read by host ...
Key fact makes life easier for
           students of virology:

           Viral genomes must make mRNA
          that ca...
David Baltimore (Nobel laureate) used this
 insight to describe a simple way to think
            about virus genomes
    ...
David Baltimore (Nobel laureate) used this
  insight to describe a simple way to think
             about virus genomes
  ...
Definitions


• (+) strand: mRNA, because it can be
  immediately translated. A strand of
  DNA of the equivalent polarity ...
The elegance of the Baltimore system




  Knowing only the nature of the viral genome,
   one can deduce the basic steps ...
The seven classes of viral
           genomes

                       • dsRNA
   • dsDNA
                     • ss (+) RNA...
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
Virology lecture #1 - What is a virus?
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Virology lecture #1 - What is a virus?

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

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  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • We live and prosper in a literal cloud of viruses. The numbers of potentially infectious particles that impinge on us daily are astronomical. Seasonal “colds,” “flu,” childhood rashes, measles, chicken pox, and mumps, as well as AIDS and Ebola fever, all serve notice of our vulnerability.
  • Virology lecture #1 - What is a virus?

    1. 1. Biology W3310 Virology
    2. 2. Biology W3310 Virology • Prof. Vincent Racaniello, Ph.D.
    3. 3. Biology W3310 Virology • Prof. Vincent Racaniello, Ph.D. - vrr1@columbia.edu
    4. 4. Biology W3310 Virology • Prof. Vincent Racaniello, Ph.D. - vrr1@columbia.edu - twitter.com/@profvrr
    5. 5. Biology W3310 Virology • Prof. Vincent Racaniello, Ph.D. - vrr1@columbia.edu - twitter.com/@profvrr • Prof. Saul Silverstein, Ph.D.
    6. 6. Biology W3310 Virology • Prof. Vincent Racaniello, Ph.D. - vrr1@columbia.edu - twitter.com/@profvrr • Prof. Saul Silverstein, Ph.D. - sjs6@columbia.edu
    7. 7. 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
    8. 8. 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
    9. 9. Biology W3310 Virology
    10. 10. Biology W3310 Virology • Courseworks or http://microbiology.columbia.edu/ w3310.html
    11. 11. Biology W3310 Virology • Courseworks or http://microbiology.columbia.edu/ w3310.html - Schedule, readings, screencasts
    12. 12. Biology W3310 Virology • Courseworks or http://microbiology.columbia.edu/ w3310.html - Schedule, readings, screencasts • Textbook: Principles of Virology, Third Edition, ASM Press
    13. 13. 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
    14. 14. 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
    15. 15. All living things survive in a sea of viruses
    16. 16. All living things survive in a sea of viruses • We eat and breathe billions of them regularly
    17. 17. 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
    18. 18. 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
    19. 19. 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
    20. 20. 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
    21. 21. 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
    22. 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 -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
    23. 23. The number of viruses impinging on us is staggering
    24. 24. The number of viruses impinging on us is staggering More than 1030 bacteriophage particles in the world’s water supply!
    25. 25. 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)
    26. 26. 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!
    27. 27. 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)
    28. 28. Andromeda Galaxy - 2.5 million light years away
    29. 29. •Whales are commonly infected with a tiny virus of the Caliciviridae family
    30. 30. •Whales are commonly infected with a tiny virus of the Caliciviridae family •These whale diarrhea viruses cause rashes, blisters, gastroenteritis in marine mammals
    31. 31. •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
    32. 32. •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!!
    33. 33. There are ~1016 HIV genomes on the planet today
    34. 34. 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,
    35. 35. Amazingly, the vast majority of the viruses that infect us have little or no impact on our health
    36. 36. 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
    37. 37. 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
    38. 38. 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
    39. 39. How ‘infected’ are we?
    40. 40. How ‘infected’ are we? •Each of you in this room is probably infected with at least 2 of the 9 known herpesviruses:
    41. 41. 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)
    42. 42. 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
    43. 43. Every one of your cells is infected with viruses
    44. 44. 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
    45. 45. 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
    46. 46. 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
    47. 47. 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?
    48. 48. You are a reservoir for viruses that have set up residence in your lungs and gastrointestinal tract (plus a few other places)
    49. 49. 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
    50. 50. 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
    51. 51. 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
    52. 52. Viruses are amazing This course will teach you why
    53. 53. •This course is designed to help you see the ‘big picture’ of virology
    54. 54. •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
    55. 55. •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
    56. 56. •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
    57. 57. •Virology requires that you know a little about almost every subject in biology
    58. 58. •Virology requires that you know a little about almost every subject in biology •Virology constantly tests your ability to think and pull information together
    59. 59. •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.
    60. 60. •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
    61. 61. 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
    62. 62. •Viruses are a significant part of the ecosystem, infecting every living thing
    63. 63. •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’
    64. 64. •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
    65. 65. The Big Picture: A common strategy, unity in diversity
    66. 66. 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:
    67. 67. 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
    68. 68. 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
    69. 69. 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
    70. 70. Why study virology if this is all there is to it?
    71. 71. 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
    72. 72. 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:
    73. 73. 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
    74. 74. 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
    75. 75. 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
    76. 76. 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
    77. 77. 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
    78. 78. Nevertheless, there is an underlying simplicity and order to viruses because of two simple
    79. 79. 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
    80. 80. 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
    81. 81. As viruses are obligate molecular parasites, every solution must reveal something about the host as well as the virus
    82. 82. Be careful: Avoid anthropomorphic analyses
    83. 83. Be careful: Avoid anthropomorphic analyses Viruses do NOT think!
    84. 84. Be careful: Avoid anthropomorphic analyses Viruses do NOT think! (or employ, ensure, exhibit, display, etc...)
    85. 85. 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
    86. 86. 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
    87. 87. 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
    88. 88. Viruses are simple ‘Darwinian Machines’
    89. 89. Viruses are simple ‘Darwinian Machines’ • There is no better model for the concept of ‘survival of the fittest’
    90. 90. 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
    91. 91. 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
    92. 92. 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
    93. 93. How is the balance of host and virus survival established?
    94. 94. 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
    95. 95. After this course is over, you will have:
    96. 96. After this course is over, you will have: • Significantly better insight into how cells work and interact
    97. 97. 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
    98. 98. 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
    99. 99. 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
    100. 100. 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
    101. 101. 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
    102. 102. Assertions you should be able to defend when the course is over
    103. 103. 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
    104. 104. 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
    105. 105. 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
    106. 106. 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
    107. 107. • This course will emphasize animal viruses, with some discussion of bacterial viruses
    108. 108. • This course will emphasize animal viruses, with some discussion of bacterial viruses • Many viruses will be ignored simply because of time constraints
    109. 109. How old are viruses?
    110. 110. How old are viruses? • With few exceptions there is no fossil record
    111. 111. How old are viruses? • With few exceptions there is no fossil record • Estimates of molecular evolution place some viruses among the dinosaurs
    112. 112. 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
    113. 113. Ancient references to viral 700 B.C. 1580-1350 B.C.
    114. 114. • Prevention of virus infections in practice since the 11th century without knowledge of agent
    115. 115. • 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
    116. 116. • 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)
    117. 117. • 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
    118. 118. Concept of microorganisms
    119. 119. Concept of microorganisms • Leeuwenhoek (1632 - 1723) made microscopes, discovered “wee animalcules”, lead to acceptance of microorganisms
    120. 120. 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
    121. 121. 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
    122. 122. Pasteur’s swan-neck flask http://www.twiv.tv/2009/06/07/twiv-35-much-achoo-about-nothing/
    123. 123. Virus discovery - filterable agents
    124. 124. Virus discovery - filterable agents • 1892 - Ivanovsky - found the agent of tobacco mosaic disease passes through filters that retain bacteria
    125. 125. 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
    126. 126. Virus discovery
    127. 127. Virus discovery • 1898 - Loeffler & Frosch - agent of foot & mouth disease is filterable
    128. 128. 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
    129. 129. 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)
    130. 130. 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
    131. 131. Virus From the Latin meaning toxin or poison
    132. 132. Virus From the Latin meaning toxin or poison virion = infectious particle
    133. 133. We know many details about Chemical formula for poliovirus: C332,652 H492,388 N98,245 O131,196 P7,501 S2,340
    134. 134. What is a virus?
    135. 135. What is a virus? • A virus is a very small, infectious, obligate intracellular parasite
    136. 136. 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)
    137. 137. 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
    138. 138. 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
    139. 139. 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
    140. 140. Are viruses alive? http://www.virology.ws/2009/11/23/are-viruses-alive/
    141. 141. Viruses are very small Carbon atom ribosome HIV-1 phage TMV poliovirus myosin actin 1,000,000x E. coli 100,000x
    142. 142. 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
    143. 143. Very small?
    144. 144. Very small? • Mimivirus: largest known virus
    145. 145. Very small? • Mimivirus: largest known virus • host: Amoebae
    146. 146. Very small? • Mimivirus: largest known virus • host: Amoebae • 500 nm particle + 125 nm fibers = 750 nm or 0.75 μm
    147. 147. 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
    148. 148. 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
    149. 149. Mimivirus particles can be seen by light microscopy giantvirus.or g
    150. 150. Defining viral attributes
    151. 151. Defining viral attributes • The genome is comprised of either DNA or RNA
    152. 152. 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
    153. 153. 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
    154. 154. 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
    155. 155. 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
    156. 156. 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
    157. 157. 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
    158. 158. Virus classification • Classical hierarchical system: Kingdom Phylum Class Order Family Genus Species
    159. 159. Virus classification
    160. 160. Virus classification • Viruses are classified according to four main characteristics:
    161. 161. Virus classification • Viruses are classified according to four main characteristics: - nature of nucleic acid in virion
    162. 162. Virus classification • Viruses are classified according to four main characteristics: - nature of nucleic acid in virion - symmetry of protein shell (capsid)
    163. 163. 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)
    164. 164. 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
    165. 165. 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
    166. 166. Family: Picornaviridae (picornavirus from ViralZone http://www.expasy.ch/viralzone/
    167. 167. http://
    168. 168. • 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!
    169. 169. 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
    170. 170. Alfred Hershey & Margaret Chase, 1952
    171. 171. 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
    172. 172. 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
    173. 173. David Baltimore (Nobel laureate) used this insight to describe a simple way to think about virus genomes - a major unifying principle in virology
    174. 174. 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
    175. 175. 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
    176. 176. 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
    177. 177. The seven classes of viral genomes • dsRNA • dsDNA • ss (+) RNA • gapped dsDNA • ss (-) RNA • ssDNA • ss (+) RNA with DNA intermediate
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