What is a virus?

Lecture 1
Biology 3310/4310
Virology
Spring 2017

“There is an intrinsic simplicity of nature and the ultimate contribution of science resides
in the discovery of unifying and simplifying generalizations, rather than in the description
of isolated situations - in the visualization of simple, overall patterns rather than in the
analysis of patchworks”
--SALVADOR LURIA
 Biology 3310/4310
Virology

• Prof. Vincent Racaniello, Ph.D.

- [email protected]
- twitter.com/@profvrr
- plus.google.com/+VincentRacaniello
- facebook.com/thisweekinvirology
• TA: Amy Rosenfeld, Ph.D.
- [email protected]
 Biology 3310/4310
Virology

• courseworks.columbia.edu
- Schedule, lecture slides, study
questions, readings, video, quiz, grading
• virology.ws/course
 Biology 3310/4310
Virology

RecommendedTextbook: Principles of Virology

Fourth Edition, ASM Press

Sample chapter on Courseworks

 Biology 3310/4310
Virology

www.virology.ws microbe.tv/twiv
 Biology 3310/4310
Virology

• Weekly quiz (Courseworks)

• 4 exams (2/8, 3/6, 4/5, final)
• Discussion sessions (4310 only)
• Reviews before exams (TA Amy)
 Biology 3310/4310
Virology

• Office hours: Thursdays 4-6 PM, HHSC

1310B, 701 W. 168th (Medical Center)
• Open format
• Appointments
• Questions during lecture
• https://piazza.com/columbia/spring2017/
biol33104310/home
 We live and prosper in a cloud of viruses

• Viruses infect all living things

• We eat and breathe billions of virions regularly
• We carry viral genomes as part of our own genetic
material

Virology Lectures • Prof. Vincent Racaniello • Columbia University

 The number of viruses on Earth is staggering
More than 1030 bacteriophage
particles in the world’s waters!

• 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 100

million light years!



http://www.phagehunter.org/2008/09/how-far-do-
those-phages-stretch.html


Virology Lectures • Prof. Vincent Racaniello • Columbia University

 1013

Virology Lectures • Prof. Vincent Racaniello • Columbia University

Viruses are not just purveyors of bad news

More viruses in a liter of coastal seawater

than people on Earth

94%

Virology Lectures • Prof. Vincent Racaniello • Columbia University

 There are ~1016 HIV genomes
on the planet today

Virology Lectures • Prof. Vincent Racaniello • Columbia University

 How ‘infected’ are we?

• HSV-1, HSV-2, VZV, HCMV


EBV, HHV-6, HHV-7, HHV-8

• Once infected, it is for life

Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
 Microbiome

Virology Lectures • Prof. Vincent Racaniello • Columbia University http://linxc10.wix.com/microbes#!the-microbiome/chht

 Virome

Intervirology 2013;56:395 Science News 11 January 2014

Virology Lectures • Prof. Vincent Racaniello • Columbia University

 3.2 billion bases
Virology Lectures • Prof. Vincent Racaniello • Columbia University
 Amazingly, the vast
majority of the
viruses that infect us
have little or no
impact on our health
or well being

Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
 Not all viruses make you sick...

Virology Lectures • Prof. Vincent Racaniello • Columbia University

 The good viruses

Virology Lectures • Prof. Vincent Racaniello • Columbia University

 An enteric virus can replace the beneficial
function of commensal bacteria

Virology Lectures • Prof. Vincent Racaniello • Columbia University doi: 10.1038/nature13960

 Viruses are amazing

Virology is an integrative science

Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
 Course goals
• 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


• You will learn the fundamentals about these

molecular wizards that amaze the informed
and frighten the uninformed

Virology Lectures • Prof. Vincent Racaniello • Columbia University

Virology Lectures • Prof. Vincent Racaniello • Columbia University
 I will use Socrative
to deliver quizzes during lectures
Go to:
b.socrative.com/login/student
room number: virus
Which statement is true?

1. All viruses make us sick and can be lethal

2. Our immune system can manage most viral infections
3. Humans are usually infected with one virus at a time
4. The press is usually correct in their virology reporting
5. Our immune system cannot handle most viral infections

1
 What is a virus?

An infectious, obligate intracellular

parasite comprising genetic material
(DNA or RNA) surrounded by a protein
coat and/or a membrane

Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
 As virions are obligate molecular parasites, every solution
must reveal something about the host as well as the virus

Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
 Are viruses alive?

http://www.virology.ws/are-viruses-alive/
Virology Lectures • Prof. Vincent Racaniello • Columbia University
 The virus and the virion

A virus is an organism with two phases

virion infected cell

Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
 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 • Prof. Vincent Racaniello • Columbia University

 Viruses are very small Carbon atom

myosin actin
1,000,000x

E. coli 100,000x
Virology Lectures • Prof. Vincent Racaniello • Columbia University
Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
 How many viruses can fit on the head
of a pin?

2 mm = 2000 microns
• 500 million rhinoviruses
• When you sneeze, you fire an aerosol that contains
enough viruses to infect thousands
Virology Lectures • Prof. Vincent Racaniello • Columbia University
 Not as small as we once thought!

Virology Lectures • Prof. Vincent Racaniello • Columbia University

 Pandoravirus

Virology Lectures • Prof. Vincent Racaniello • Columbia University DOI: 10.1126/science.1239181

 Viruses replicate by
assembly of pre-
formed components
into many particles

Make the parts,

assemble the final product

Not binary fission like cells

Virology Lectures • 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. Viruses must assemble using pre-formed components

2. Bacteria do not replicate via binary fission as viruses do
3. Bacteria must assemble using pre-formed components
4. Viruses do not have an "eclipse" period
5. Viruses replicate by binary fission

2
 How old are viruses?

Orthoceras, a nautiloid cephalopod, 488 Ma

Nobu Tamura (http://spinops.blogspot.com)

• Estimates of molecular evolution suggest marine

origin of some retroviruses >450 Ma, Ordovician
period
• Likely originated billions of years ago - before
cells?
Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
 Ancient references to viral diseases

700 B.C.
1580-1350 B.C.
Virology Lectures • 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 • Prof. Vincent Racaniello • Columbia University

 Concept of microorganisms

• Leeuwenhoek (1632 - 1723)

• Pasteur (1822 - 1895)
• Koch (1843-1910)

Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
 Virus discovery - filterable agents

• 1892 - Ivanovsky
• 1898 - Beijerinck: contagium vivum fluidum
• Virus: slimy liquid, poison

Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
 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)

Virology Lectures • Prof. Vincent Racaniello • Columbia University

 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

Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
 Go to:

b.socrative.com/login/student
room number: virus

Which is a key concept first discovered about viruses that

distinguished them from other microorganisms?

1. They were too large to pass through a 0.2 micron filter

2. They could replicate only in broth
3. They made tobacco plants sick
4. They were small enough to pass through a 0.2 micron filter
5. None of the above

3
Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
 We know many details about viruses

Chemical formula for poliovirus:

C332,652 H492,388 N98,245 O131,196 P7,501 S2,340

Virology Lectures • Prof. Vincent Racaniello • Columbia University
 Virus classification

• Nature and sequence of nucleic acid in virion

• Symmetry of protein shell (capsid)
• Presence or absence of lipid membrane
(envelope)
• Dimensions of virion & capsid

Virology Lectures • Prof. Vincent Racaniello • Columbia University ©Principles of Virology, ASM Press
 Virus classification
http://ictvonline.org/
Classical hierarchical system:
Kingdom
Phylum
Class
Order (-virales)
Family (-viridae) Filoviridae (filovirus family)
Genus (-virus) Ebolavirus
Species
Zaire ebolavirus
Virology Lectures • Prof. Vincent Racaniello • Columbia University
 Virus discovery

Analyzed RNA from 220 vertebrates species,

found 1,445 new viruses.
Virology Lectures • Prof. Vincent Racaniello • Columbia University http://www.nature.com/nature/journal/v540/n7634/full/nature20167.html
 Why do we care?

• Viruses outnumber cellular life by at least 10:1:

the greatest biodiversity on Earth
• Viruses drive global cycles
• Beneficial
• Sources of new pathogens?

Virology Lectures • Prof. Vincent Racaniello • Columbia University

 There is an underlying simplicity and
order to viruses because of two
simple facts

• 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