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INTRODUCTION TO VIROLOGY
CHARMAINE C MIRANDILLA
WHAT IS
VIRUS?
-Smallest infectious
agent
- a minuscule, acellular,
infectious agent
usually having one or
several pieces of
nucleic acid—either
DNA or RNA.
Why do we study Viruses?
1. Virus are everywhere
● Viruses infect all living
things
● We regularly eat and
breathe billions of virus
particles
● We carry viral genomes as
part of our own genetic
material
Did you Know?
● There are more than 10^ 30
Bacteriophage in the world's
oceans
● Whales are infected with
Caliciviridae that causes
rashes, blisters, intestinal
problems and they excrete it
10^13 calicivirus particles
Why do we study Viruses?
2. Viruses can Cause Human Disease
● Small pox
● Influenza
● Hepatitis
● HIV
● Cervical cancer
● COVID 19
Why do we study Viruses?
4. Virus can be Beneficial
● Viral infections in the ocean kill 20 to 40% of marine
microbes daily, converting these living organisms into
particulate matter, and in so doing release essential
nutrients that supply phytoplankton
● Infection of Hepatitis G in patient with HIV can
decrease the progression of disease
● Murine herpesvirus are resistant with Listeria
monocytogenes and Yersinia pestis
● Can stimulate Immune System
Why do we study Viruses?
5. Viruses are Unique Tools to
Study Biology
● Bacteriophage is
Foundation of Molecular
Biology
● Tobacco mosaic virus was a
landmark in structural
biology
● Development of
Recombinant DNA
Technology
● Use of Viral Vector
Introduction_to_Virology_Medicaltechnology
Introduction_to_Virology_Medicaltechnology
Introduction_to_Virology_Medicaltechnology
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
Viruses are passive agents!
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
Viruses replicate by assembly of
pre-formed components into
particles
many
Make the parts,
assemble the final product
Not binary fission like cells
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
Go to:
b.socrative.com/login/student
room number: virus
Which of the following is true concerning bacterial vs. viral replication?
1.
2.
3.
4.
5.
Viruses must assemble using pre-formed components
Bacteria do not replicate via binary fission
Bacteria must assemble using pre-formed
Viruses do not have an "eclipse" period
Viruses replicate by binary fission
as viruses do
components
2
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
How old are viruses?
Orthoceras, a nautiloid cephalopod, 488 Ma
Nobu Tamura (http://spinops.blogspot.com)
• Estimates of molecular evolution
retroviruses >450 Ma, Ordovician
Likely originated billions of years
suggest marine
period
origin of some
• ago - before cells?
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
Immunization
• Variolation - China (11th century), Lady Montagu
(1700s)
No knowledge of agent
Survivors of smallpox protected against disease
1790s - experiments by Edward Jenner in England
establish vaccination
•
•
•
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
Concept of microorganisms
•
•
•
Leeuwenhoek (1632 -
Pasteur (1822 - 1895)
1723)
Koch (1843-1910)
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
The evolving concept of virus
• As early as 1728, ‘virus’ was used to describe an
infectious disease
agent that causes
•
•
Virus = Latin, poison; so thought to be liquids
Pasteur (1822 - 1895): “Every virus is a microbe”
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
Key event: Chamberland filter
• Developed a porcelain filter to remove bacteria
from drinking water
• Pasteur
thought
found that rabies agent passed through it,
it was a small bacterium
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
Virology Lectures 2019 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
Filterable viruses
•
•
1898 - Loeffler & Frosch - agent of foot & mouth disease is filterable
Key concept: agents not only small,
in broth
but replicate only in the host, not
•
•
0.2 micron filters (μm, one millionth of a meter)
Still thought to be liquids
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
Filterable virus discovery
•
•
•
•
•
•
•
1901
1903
1906
1908
1911
1915
1933
-
-
-
-
-
-
-
first human virus,
rabies virus
variola virus
chicken leukemia
yellow fever virus
virus, poliovirus
Rous sarcoma virus
bacteriophages
influenza virus
©Principles of Virology, ASM Press
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
1939 - Viruses are not liquids!
microscope
•
•
Helmut Ruska built first electron 1933
First EM of bacteriophage, 1939
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
Key 1939 experiment proved that viruses
were not simply small bacteria
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
©Principles of Virology, ASM Press
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
We know many details about viruses
Virology Lectures 2019 • Prof. Vincent Racaniello • Columbia University
Chemical formula for poliovirus:
C
332,652
H
492,388
N
98,245
O
131,196
P
7,501
S
2,340
Virus classification
•
•
•
•
Nature and sequence of nucleic acid
Symmetry of protein shell (capsid)
in virion
Presence or
Dimensions
absence of lipid
of virus particle
membrane (envelope)
©Principles of Virology, ASM Press
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
Virus classification
http://ictvonline.org/
Classical hierarchical
Kingdom
Phylum
Class
Order (-virales)
system:
Family (-viridae)
Genus (-virus)
Species*
Filoviridae
Ebolavirus
(filovirus family)
Zaire ebolavirus
Virus discovery - Once driven only by disease
Analyzed RNA from 220 invertebrate species, found 1,445 new viruses
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University http://www.nature.com/nature/journal/v540/n7634/full/nature20167.html
CHARACTERISTIC OF VIRUSES
STRUCTURE OF VIRUS
●Viral genome: RNA or DNA
●Capsid: protein coat that
encloses the genome
○Capsid + genome =
Nucleocapsid
● Capsomere
○ represent clusters of
polypeptides seen in
icosahedral
●The entire virus particle is
called virion
VIRAL GENOME
●Composed of either RNA or DNA
●4 category based on the virus
genome
○ Double stranded DNA
○ Single stranded DNA
○ Double stranded RNA
■ Fungal viruses
○ Single stranded RNA
■ Plant viruses
●Basis of molecules
○ Linear
○ Circular
VIRAL PROTEIN
●As the size of genome increases the number of protein
increases.
○Structural protein
■ Protects the virus genome
■ Attachment of the virion to a host cell
■ Fusion of the virion envelope to cell membrane
○Non structural Protein
■ enzymes, e.g. protease, reverse transcriptase
■ transcription factors
■ primers for nucleic acid replication
■ interference with the immune response of the host
CAPSID
●A Protein coat that encloses the genome
●Function:
○ the protection of the genome
○ To recognize and attach to a host cell.
●Capsomere
○ Cluster of polypeptide common in icosahedral
viruses
FUNCTION OF CAPSID
●Protects the viral genome
● Is the site of receptors necessary for naked viruses to initiate infection
● Stimulates antibody production
●Is the site of antigenic determinants important in some serologic tests
Symmetry or
Morphology
●Helical
○ Complete virion
○ Capsomere are in bagel shape
○ Rod shape capsid
●Icosahedral
○ Cube like
●Complex
○ Non forming symmetry
○ Example Poxviridae
Introduction_to_Virology_Medicaltechnology
OUTERMEMBRANE
ENVELOPE
●Phospholipid labile covering
●Susceptible to inactivation
○ High temperature
○ Extreme pH
○ Chemical
●Host origin
●Peplomer (Spikes)
○ Virus encoded glycoprotein
●Cannot infect GI tract.
NAKED/ NON ENVELOPE
•Heat resistant
•Lipid membrane
Introduction_to_Virology_Medicaltechnology
CLASSIFICATION OF VIRUSES
●Virion Morphology
○ Based on Size, shape, type of symmetry, presence or absence of peplomer
●Virus genome (Baltimore Classification)
○ Type of Nucleic Acid (DNA or RNA)
○ Whether it is linear or circular
○ Sense (positive, negative or ambisense)
○ Size of genome
○ Strandedness (Double or Single stranded)
●Physicochemical properties
●Virus Protein
CLASSIFICATION OF VIRUSES: DNA
VIRUSES
●Herpesviridae
●Hepadnaviridae
●Poxviridae
●Parvoviridae
●Adenoviridae
●Papovaviridae
•All DNA are Double
Stranded except
Parvoviridae
•All DNA viruses are
icosahedral except
Poxviridae
•Enveloped
• Herpesviridae
• Hepadnaviridae
• Poxviridae
Introduction_to_Virology_Medicaltechnology
CLASSIFICATION OF VIRUSES: RNA
VIRUSES
●Picornaviridae
●Caliciviridae
●Reoviridae
●Retroviridae
●Togaviridae
●Flaviviridae
●Bunyaviridae
●Arenaviridae
•Filoviridae
•Paramyxoviridae
•Orthomyxoviridae
•Reoviridae
•Retroviridae
•Rhabdoviridae
CLASSIFICATION OF VIRUSES: RNA
VIRUSES
●All RNA viruses are Single Stranded, Helical and Envelope
●All are Single stranded except Reoviridae
●All are Helical except
○ Picronaviridae
○ Caliciviridae
○ Reoviridae
○ Retroviridae
○ Togaviridae
○ Flaviviridae
CLASSIFICATION OF VIRUSES: RNA
VIRUSES
●All are envelope except Picornaviridae,
Caliciviridae and Reoviridae
●Largest: Paramyxoviridae
●Smallest: Picornaviridae
●Arthropod borne or vector borne
○ Bunyaviridae
○ Flaviviridae
○ Togaviridae
●Replicate in Nucleus
○ Orthomyxoviridae and Retroviridae
Introduction_to_Virology_Medicaltechnology
BALTIMORE CLASSIFICATION
There is an underlying simplicity and order
to viruses because of two simple facts
• All viral genomes are obligate molecular
function after they replicate in a cell
parasites that can only
• All viruses must make mRNA that can be translated by host
synthesis
ribosomes:
machinery
they are all parasites of the host protein
Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University

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Introduction_to_Virology_Medicaltechnology

  • 2. WHAT IS VIRUS? -Smallest infectious agent - a minuscule, acellular, infectious agent usually having one or several pieces of nucleic acid—either DNA or RNA.
  • 3. Why do we study Viruses? 1. Virus are everywhere ● Viruses infect all living things ● We regularly eat and breathe billions of virus particles ● We carry viral genomes as part of our own genetic material
  • 4. Did you Know? ● There are more than 10^ 30 Bacteriophage in the world's oceans ● Whales are infected with Caliciviridae that causes rashes, blisters, intestinal problems and they excrete it 10^13 calicivirus particles
  • 5. Why do we study Viruses? 2. Viruses can Cause Human Disease ● Small pox ● Influenza ● Hepatitis ● HIV ● Cervical cancer ● COVID 19
  • 6. Why do we study Viruses? 4. Virus can be Beneficial ● Viral infections in the ocean kill 20 to 40% of marine microbes daily, converting these living organisms into particulate matter, and in so doing release essential nutrients that supply phytoplankton ● Infection of Hepatitis G in patient with HIV can decrease the progression of disease ● Murine herpesvirus are resistant with Listeria monocytogenes and Yersinia pestis ● Can stimulate Immune System
  • 7. Why do we study Viruses? 5. Viruses are Unique Tools to Study Biology ● Bacteriophage is Foundation of Molecular Biology ● Tobacco mosaic virus was a landmark in structural biology ● Development of Recombinant DNA Technology ● Use of Viral Vector
  • 11. 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 Viruses are passive agents! Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
  • 12. Viruses replicate by assembly of pre-formed components into particles many Make the parts, assemble the final product Not binary fission like cells Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
  • 13. Go to: b.socrative.com/login/student room number: virus Which of the following is true concerning bacterial vs. viral replication? 1. 2. 3. 4. 5. Viruses must assemble using pre-formed components Bacteria do not replicate via binary fission Bacteria must assemble using pre-formed Viruses do not have an "eclipse" period Viruses replicate by binary fission as viruses do components 2 Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
  • 14. How old are viruses? Orthoceras, a nautiloid cephalopod, 488 Ma Nobu Tamura (http://spinops.blogspot.com) • Estimates of molecular evolution retroviruses >450 Ma, Ordovician Likely originated billions of years suggest marine period origin of some • ago - before cells? Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
  • 15. Immunization • Variolation - China (11th century), Lady Montagu (1700s) No knowledge of agent Survivors of smallpox protected against disease 1790s - experiments by Edward Jenner in England establish vaccination • • • Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
  • 16. Concept of microorganisms • • • Leeuwenhoek (1632 - Pasteur (1822 - 1895) 1723) Koch (1843-1910) Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
  • 17. The evolving concept of virus • As early as 1728, ‘virus’ was used to describe an infectious disease agent that causes • • Virus = Latin, poison; so thought to be liquids Pasteur (1822 - 1895): “Every virus is a microbe” Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
  • 18. Key event: Chamberland filter • Developed a porcelain filter to remove bacteria from drinking water • Pasteur thought found that rabies agent passed through it, it was a small bacterium Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
  • 19. Virology Lectures 2019 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
  • 20. Filterable viruses • • 1898 - Loeffler & Frosch - agent of foot & mouth disease is filterable Key concept: agents not only small, in broth but replicate only in the host, not • • 0.2 micron filters (μm, one millionth of a meter) Still thought to be liquids Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
  • 21. Filterable virus discovery • • • • • • • 1901 1903 1906 1908 1911 1915 1933 - - - - - - - first human virus, rabies virus variola virus chicken leukemia yellow fever virus virus, poliovirus Rous sarcoma virus bacteriophages influenza virus ©Principles of Virology, ASM Press Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
  • 22. Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
  • 23. 1939 - Viruses are not liquids! microscope • • Helmut Ruska built first electron 1933 First EM of bacteriophage, 1939 Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
  • 24. Key 1939 experiment proved that viruses were not simply small bacteria Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
  • 25. ©Principles of Virology, ASM Press Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
  • 26. We know many details about viruses Virology Lectures 2019 • Prof. Vincent Racaniello • Columbia University Chemical formula for poliovirus: C 332,652 H 492,388 N 98,245 O 131,196 P 7,501 S 2,340
  • 27. Virus classification • • • • Nature and sequence of nucleic acid Symmetry of protein shell (capsid) in virion Presence or Dimensions absence of lipid of virus particle membrane (envelope) ©Principles of Virology, ASM Press Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University
  • 28. Virus classification http://ictvonline.org/ Classical hierarchical Kingdom Phylum Class Order (-virales) system: Family (-viridae) Genus (-virus) Species* Filoviridae Ebolavirus (filovirus family) Zaire ebolavirus
  • 29. Virus discovery - Once driven only by disease Analyzed RNA from 220 invertebrate species, found 1,445 new viruses Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University http://www.nature.com/nature/journal/v540/n7634/full/nature20167.html
  • 31. STRUCTURE OF VIRUS ●Viral genome: RNA or DNA ●Capsid: protein coat that encloses the genome ○Capsid + genome = Nucleocapsid ● Capsomere ○ represent clusters of polypeptides seen in icosahedral ●The entire virus particle is called virion
  • 32. VIRAL GENOME ●Composed of either RNA or DNA ●4 category based on the virus genome ○ Double stranded DNA ○ Single stranded DNA ○ Double stranded RNA ■ Fungal viruses ○ Single stranded RNA ■ Plant viruses ●Basis of molecules ○ Linear ○ Circular
  • 33. VIRAL PROTEIN ●As the size of genome increases the number of protein increases. ○Structural protein ■ Protects the virus genome ■ Attachment of the virion to a host cell ■ Fusion of the virion envelope to cell membrane ○Non structural Protein ■ enzymes, e.g. protease, reverse transcriptase ■ transcription factors ■ primers for nucleic acid replication ■ interference with the immune response of the host
  • 34. CAPSID ●A Protein coat that encloses the genome ●Function: ○ the protection of the genome ○ To recognize and attach to a host cell. ●Capsomere ○ Cluster of polypeptide common in icosahedral viruses
  • 35. FUNCTION OF CAPSID ●Protects the viral genome ● Is the site of receptors necessary for naked viruses to initiate infection ● Stimulates antibody production ●Is the site of antigenic determinants important in some serologic tests
  • 36. Symmetry or Morphology ●Helical ○ Complete virion ○ Capsomere are in bagel shape ○ Rod shape capsid ●Icosahedral ○ Cube like ●Complex ○ Non forming symmetry ○ Example Poxviridae
  • 38. OUTERMEMBRANE ENVELOPE ●Phospholipid labile covering ●Susceptible to inactivation ○ High temperature ○ Extreme pH ○ Chemical ●Host origin ●Peplomer (Spikes) ○ Virus encoded glycoprotein ●Cannot infect GI tract. NAKED/ NON ENVELOPE •Heat resistant •Lipid membrane
  • 40. CLASSIFICATION OF VIRUSES ●Virion Morphology ○ Based on Size, shape, type of symmetry, presence or absence of peplomer ●Virus genome (Baltimore Classification) ○ Type of Nucleic Acid (DNA or RNA) ○ Whether it is linear or circular ○ Sense (positive, negative or ambisense) ○ Size of genome ○ Strandedness (Double or Single stranded) ●Physicochemical properties ●Virus Protein
  • 41. CLASSIFICATION OF VIRUSES: DNA VIRUSES ●Herpesviridae ●Hepadnaviridae ●Poxviridae ●Parvoviridae ●Adenoviridae ●Papovaviridae •All DNA are Double Stranded except Parvoviridae •All DNA viruses are icosahedral except Poxviridae •Enveloped • Herpesviridae • Hepadnaviridae • Poxviridae
  • 43. CLASSIFICATION OF VIRUSES: RNA VIRUSES ●Picornaviridae ●Caliciviridae ●Reoviridae ●Retroviridae ●Togaviridae ●Flaviviridae ●Bunyaviridae ●Arenaviridae •Filoviridae •Paramyxoviridae •Orthomyxoviridae •Reoviridae •Retroviridae •Rhabdoviridae
  • 44. CLASSIFICATION OF VIRUSES: RNA VIRUSES ●All RNA viruses are Single Stranded, Helical and Envelope ●All are Single stranded except Reoviridae ●All are Helical except ○ Picronaviridae ○ Caliciviridae ○ Reoviridae ○ Retroviridae ○ Togaviridae ○ Flaviviridae
  • 45. CLASSIFICATION OF VIRUSES: RNA VIRUSES ●All are envelope except Picornaviridae, Caliciviridae and Reoviridae ●Largest: Paramyxoviridae ●Smallest: Picornaviridae ●Arthropod borne or vector borne ○ Bunyaviridae ○ Flaviviridae ○ Togaviridae ●Replicate in Nucleus ○ Orthomyxoviridae and Retroviridae
  • 48. There is an underlying simplicity and order to viruses because of two simple facts • All viral genomes are obligate molecular function after they replicate in a cell parasites that can only • All viruses must make mRNA that can be translated by host synthesis ribosomes: machinery they are all parasites of the host protein Virology Lectures 2020 • Prof. Vincent Racaniello • Columbia University