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Spring 20021
Lecture # 1: Course Introduction
•I. Instructor and Background–
Dr. Richard Kuhn–
–B-129 Lilly Hall
–494-1164
–O
ffice Hours - Wednesday 10:30 - 11:30
•II. O
bjective: To use viruses as a vehicle to:–
1) Study disease–
2) Examine how viruses provide ideal m
odel systems for unraveling how the
cell itself functions.–
3) Demonstrate the potential of using viruses to deliver genes and other novel
therapeutic approaches
•III. W
hat are the requirements for taking and passing this course?
–1) Core biology courses
–2) The ability to blend fundam
ental principles from biology, chem
istry, andphysics
–3) A little curiosity and som
e work
Spring 20022
•IV. Course syllabus:
–1. Course lim
ited to eukaryotic host-viral systems
–2. Two different phases to the course:
•a) Introduction to viral processes
•b) An exam
ination of specific viral systems
•V. Description of class m
echanics–
1. Lecture format:
•a. Lecture with research exam
ples•
b. Straight mem
orization will not help you: apply principles!•
c. Ask questions or I will ask questions of you–
2. Texts•
Viruses and Human Disease (Strauss & Strauss) 2002
•Fundam
entals of Molecular Virology (Acheson) 2002
•Reference: Principles of Virology (Flint, Enquist, Krug, Racaniello, Skalka) 1999 -Not required but good reading and diagram
s–
3. Lecture notes: will be available as PDFs on the web.–
4. Exams: 3 exam
s equal weight (33% each exam
).•
a. Final is not cumulative (covers only last 1/3)
•b. Form
at of exams: short answer/ T/F/ thinking essays
•c. Approach to passing exam
s: apply principles
Spring 20023
Spring 20024
5IN
TR
OD
UC
TIO
N
“the p
ox”
1798
Jenner
6IN
TR
OD
UC
TIO
N
Infective
Bacteria-F
reeF
iltrate
1798
Jenner
1890
Iwanow
ski,B
eijerinck,Loeffler &F
rosch
Spring 20027
Early Discovery of Infectious A
gents
Spring 20028
Early Landmarks in V
irus ResearchD
ateV
irologistD
iscovery
late 1800’s K
ochFilterable agents, K
och’s postulates
1898Loeffler &
FroschFirst dem
onstration of a filterable animal virus, foot and m
outh virus
1901Reed
Identification of Yellow
fever virus
1909 Landsteiner &
Popper
Transmission of CN
S fluid from child to m
onkey establishes a virus as a causative agent for poliom
yelitis
1911Rous
Identified virus causing solid tumors, Rous sarcom
a virus
1931W
oodruffU
se of embryonic hen’s egg as a viral host
1933Sm
ithIsolation of Influenza
1949Enders
Nonneuronal tissue supports poliovirus replication in culture
1952D
ulbeccoD
evelopment of virus plaque assay
1952H
ershey & Chase
Nucleic acid is the genetic m
aterial
1950sSalk &
SabinD
evelopment of killed and attenuated poliovirus vaccines
1972Tem
in & Baltim
oreD
iscovery of reverse transcriptase
1984M
ontagnier & G
alloIsolation of H
IV as the causative agent for A
IDS
Spring 20029
YearN
ames
Nobel C
itation; Virus Group or Fam
ily
1946[Chem
istry]W
endell StanleyIsoation, purification and crystallization of tobacco m
osaic virus; Tobam
ovirus
1980 [Chem
istry]Paul Berg
Studies of the biochemistry of nucleic acids, w
ith particular regard to recom
binant DN
A (SV40);Polyom
aviridae
1982[Chem
sitry]A
aron KlugD
evelopment of crystallographic electron m
icroscopy and structural elucidation of biologically im
portant nucleic acid- protein com
plexes;Tobamovirus and Tym
ovirus
1951M
ax TheilerD
evelopment of yellow
fever vaccine; Flaviviridae
1954John F. Enders,Thom
as Weller,
Frederick C. Robbins
Grow
th and cultivation of poliovirus; Picornaviridae
1958Joshua Lederberg
Transforming bacteriophages
1965Francois Jacob,A
ndré Lwoff
Jacques Monod
Operons; bacteriophages
1966Francis Peyton Rous
Discovery of tum
or-producing viruses; Retroviridae
1969M
ax Delbruck,
Alfred D
. Hershey,
Salvador E. Luria
Mechanism
of virus infection in living cells; bacteriophages
1975D
avid Baltimore,
How
ard M. Tem
in,Renato D
ulbecco
Discoveries concerning the interaction betw
een tumour
viruses and the genetic material of the cell; Retroviridae
1976D
. Carleton Gajdusek
Baruch S. Blumberg
New
mechanism
s for the origin and dissemination of
infectious diseases; B with H
epadnaviridae, G w
ith prions.
1989J. M
ichael Bishop,H
arold E. Varmus
Discovery of the cellular origin of retroviral oncogenes;
Retroviridae
1993Phillip A
. SharpRichard J. Roberts
Discoveries of split (spliced) genes; A
denoviridae
1988G
eorge Hitchings
Gertrude Elion
Important principles of drug treatm
ent using nucleotide analogs (acyclovir)
1996Rolf ZinkernagelPeter D
ohertyPresentation of viral epitopes by M
HC
1997Stanley Prusiner
Prions
Nobel Prizes involving V
irology *
*A
ll prizes listed are in Physiology or Medicine except those three m
arked [Chemistry].
1978A
pplication of restriction endonucleases to the study of the genetics of SV40; Polyom
aviridaeD
aniel Nathans
****
**In these tw
o instances, the prize was shared w
ith unlisted recipients whose w
ork did not involve viruses.
Spring 200210
Spring 200211
Properties of Viruses
•A
. Definitions:
1.O
bligate intracellular parasites with a relatively sim
ple life cycle and/or2.
Viruses are entities w
hose genomes (nucleic acids) replicate inside living cells using
the cellular biosynthetic machinery and cause the synthesis of specialized elem
ents(virions) that can transfer the viral genom
e to other cells.
•B.
Small in size—
can pass through bacteriological filters
•C
. Viruses contain no enzym
es used for energy production. Some do contain
enzymes associated w
ith nucleic acid metabolism
.
•D
.V
iruses contain only one type of nucleic acid.–
1 .RN
A, double stranded or single stranded.
–2 .
DN
A, double stranded or single stranded.
–3 .
Nucleic acid is m
ain component of virion (plus coat)
–4 .
Some viruses have enzym
es in virion particles.
•E.
Replicate through an “assembly-line’ like m
echanism in the host cell—
use host cellm
etabolic machinery to synthesize all of the necessary viral com
ponents and then assemble
them into virus particle - sim
ple nature of life cycle compared to that of a eukaryotic cell.
Spring 200212
Properties of Viruses (cont’d)
•F. V
iruses known to infect nearly all organism
s.–
1. Bacteria - bacteriophages.–
2. Plants - RNA
or DN
A containing viruses as w
ell as agents called viroids.–
3. Insects - numerous viruses infect insects; certain viruses are transm
itted to bothplants and anim
als via insect vectors.–
4. Higher anim
als
Spring 200213
Levels of Analysis:
•M
olecular:»
Cell Biology»
Biochemistry
»G
enetics»
Structure
•Clinical (organism
): Pathogenesis- disease patterns- organs and tissues affected- im
mune response
•Population G
roups: Epidemiological
Spring 200214
The study of viruses require:
•1) Isolate virus and quantitate
•2) Propagate and m
anipulate–
a. animal m
odel–
replication and pathogenesis–
b. cell culture–
replication and genetics
•3) In vitro biochem
istry–
a. develop enzymatic assays
–b. study virus assem
bly–
c. determine three-dim
ensional structure of virus–
particle and viral proteins
Spring 200215
Scale of Viruses
16C
LAS
SIF
ICA
TIO
N
+ m
RN
A
- RN
A V
RN
A+-
III
+ o
r - DN
AII
DN
A+-
I
+ R
NA
- RN
AIV
+ R
NA
DN
AV
I
17C
LAS
SIF
ICA
TIO
N
+ m
RN
A
RE
TR
OV
IRID
AE
PA
RV
OV
IRID
AE
RE
OV
IRID
AE
PIC
OR
NA
VIR
IDA
ET
OG
AV
IRID
AE
FL
AV
IVIR
IDA
EC
AL
ICIV
IRID
AE
CO
RO
NA
VIR
IDA
E
BU
NY
AV
IRID
AE
AR
EN
AV
IRID
AE
RH
AB
DO
VIR
IDA
EP
AR
AM
YX
OV
IRID
AE
OR
TH
OM
YX
OV
IRID
AE
HE
PA
DN
AV
IRID
AE
PA
PO
VA
VIR
IDA
EA
DE
NO
VIR
IDA
EH
ER
PE
SV
IRID
AE
PO
XV
IRID
AE
- RN
A V
RN
A+-
III
+ o
r - DN
AII
DN
A+-
I
+ R
NA
- RN
AIV
+ R
NA
DN
AV
I
Spring 200218
Classification Scheme for A
nimal RN
A V
iruses
Spring 200219
Classification Scheme for A
nimal D
NA
Viruses
Spring 200220
Web Sites of Interest to V
irologists
•1.
http://ww
w.tulane.edu/~dm
sander/garryfavweb.htm
l–
(Has links to alm
ost all the virology sites on the web)
•2.
http://boris.qub.ac.uk/vsd/vsd6d.html
•3.
http://bilbo.bio.purdue.edu/~virusww
w/
•4.
http://ww
w.bocklabs.w
isc.edu/welcom
e.html
•5.
http://life.anu.edu.au:80/viruses/indxvir2.htm•
(A list of ICTV-approved virus names and links to virus databases)
•6.
http://life.anu.edu.au:80//./viruses/virus.html