Importance of Viruses
1. Cause many diseases in plants, animals & humans
•
Some viruses are easily controlled with a vaccine
 Mumps, Measles, Smallpox, Polio
•
Some viruses are difficult to control with a vaccine
 Retroviruses (HIV: ssRNA  dsDNA)
 Common cold, Influenza (Flu), HIV
2. Used as vectors in biotechnology
•
Used to insert therapeutic genes into a host cell
chromosome
•
Use viruses with provirus in life cycle
Herpes (dsDNA  dsDNA)
Cold sores
Herpes virus may rest inactive
inside host cells for long
periods
Adenovirus
(dsDNA)
Adenoviruses cause various
respiratory diseases
Polio Virus
(ssRNA serves as mRNA)
Polio is easily prevented with a vaccine
Measles (ssRNA template for mRNA synthesis)
Measles: a childhood disease that can be prevented with a vaccine
Couple at AIDS quilt (HIV: ssRNA  dsDNA)
HIV is very difficult to control with a vaccine
1918 Influenza epidemic (ssRNA template for mRNA synthesis)
>20 million died of the flu during WW I
A new influenza vaccine must be developed yearly
Influenza Today
Enter H5N1, the avian
flu virus
Why do new strains of influenza and bird flu arise in Asia?
Background: Influenza Virus Structure
1.
(1 of 3)
Flu viruses are named
by the type of surface
proteins
a.
Hemagglutinin
•
Helps virus
enter cell
•
Type A infects
humans, birds
and pigs
•
Type A has ~ 20
different sub
types
Flu Viruses Currently infecting...
• Humans: H1N1, H1N2, and H3N2
• Avian Flu Virus: H5N1
Background: Influenza Virus Structure
2.
Named for the type of
surface proteins
b.
•
Neuraminidase
•
Helps virus exit
cell
•
9 subtypes
Currently infecting
Humans:
H1N1, H1N2, and H3N2
(2 of 3)
Background: Influenza Virus Structure
3.
Influenza viral genome
•
•
•
ssRNA
8 segments (pieces)
One gene per segment
Avian Flu Virus: H5N1
•
•
•
Transmitted from birds to
humans
No evidence of human to
human transmission
Antiviral drugs: Tamiflu
 a neuraminidase
inhibitor
 Consequences of its
action?
(3 of 3)
Genetic Changes in Influenza Viruses
1.
Antigenic drift – due to errors in replication and lack of repair
mechanism to correct errors
•
2.
Results in ___________________ changes
Antigenic shift - reassortment of genetic materials when
concurrent infection of different viral strains occurs
•
Results in ___________________ changes
Emergence of New Influenza Subtypes: H5N1
Antigenic shift due to genome reassortment within intermediate hosts drives flu epidemics and pandemics
Solid lines: transmission demonstrated;
Dotted lines: transmission postulated but
not demonstrated.
Source: http://www.cdc.gov/ncidod/EID/vol12no01/05-1024-G1.htm
1.
Nonpathogenic H5 influenza virus: Wild fowl  domestic ducks and geese,  domestic
chickens.
2.
H5 virus became highly pathogenic in chickens  domestic ducks and geese.
3.
Highly Pathogenic H5 virus reassorted its genome with those of other influenza viruses in
aquatic birds,  spread to poultry farms, humans, and occasionally to pigs.
Where do the “new flu” viruses come from?
Antigenic Drift: mutations result in changes to the Hemagglutinin (HA) molecules
- RNA replication is error prone
- New HA types are created frequently
- Requires new vaccine every “season”
- What is a vaccine?
Vaccines: Protection against viruses
1.
What is a vaccine?
2.
Vaccines stimulate the production of memory cells
•
3.
Give long-term protection against a specific antigen
Why are vaccines ineffective against the flu virus?
•
4.
Why will this year’s flu vaccine be ineffective next year?
Why are vaccines effective against DNA viruses?
-
e.g. small pox and polio virus
Smallpox
(dsDNA  dsDNA)
Smallpox has been irradicated worldwide
due to a very successful vaccine
Why are vaccines for DNA viruses so
successful?
Hepatitis B—an RNA virus
Hepatitis B
Infections may lead to
liver cancer. Why?
Carry viral oncogene
Viruses and Cancer
Tumor Viruses: may transform normal cells into cancer cells

Hepatitis B  Liver cancer

HTLV 1  leukemia
•
•
(Human T-Cell Leukemia Virus)
Tumor viruses form a permanent provirus
Viral oncogenes
 code for growth factors
 Growth factors Stimulate cell to enter S phase
»
•
G1 or G0  S phase
Each of the following must happen for cancer to occur
 Active host oncogenes + Active viral oncogenes  cancer
 Activators of host oncogenes
•
Carcinogens, radiation, some viruses
Emerging viruses
Ebola Virus
Hanta Virus
Both viruses: ssRNA template for mRNA synthesis
Either virus usually results in death within days!
Deer Mouse: Carries Hanta virus in Feces
Mottling of Squash and Tobacco by the Mosaic Virus
Viruses can spread easily from
cell to cell via the
plasmodesmata junctions
between cells
Tobacco mosaic virus (RNA virus)
Comparing the size of a virus, a bacterium, and a eukaryotic cell
Viral Size
Millions can fit
on pinhead
Smaller than a
ribosome!
TMV
Adenovirus
Influenza virus
Viral structure
Bacteriophage T4
Viral Structure
1. Nucleic Acid + Protein Coat (Capsid)
•
•
Some viruses with Membrane (envelope) surrounding capsid

Envelope derived from plasma membrane of host cell

Helps virus infect host cell
No organelles
•
Obligate intracellular parasite
•
Lacks metabolic enzymes, ribosomes, mitochondria
•
Alone, can only infect host cell
2. Nucleic Acid: DNA or RNA
•
Single or Double Stranded
•
4 genes to a few hundred
Classes of Animal
Viruses
Grouped by Type of
Nucleic Acid
Class
Type of Nucleic Acid
I. dsDNA
Papavavirus
Papilloma (Human warts, Cervical Cancer
Adenovirus
Respiratory diseases
Herpesvirus
Herpes Simplex I (Cold sores)
Herpes Simplex II (genital sores)
Varicella zoster (chicken pox)
Poxvirus
Smallpox; cowpox
II. ssDNA
Parvovirus
Usually depends on co-infections w/adenovirus
III. dsRNA
Reovirus
Diarrhea
IV. ssRNA that serves as mRNA
Picornavirus
Poliovirus
Rhinovirus: Common cold
V. ssRNA that is a template for mRNA synthesis
Rhabdovirus
Paramyxovirus
Orthomyxovirus
Rabies
Measles, mumps
Influenza (flu)
VI. ssRNA that serves as a template for DNA synthesis
Retrovirus
HIV (AIDS virus)
RNA tumor viruses (e.g. leukemia viruses)
Host Range
Host cell Recognition
•
Complementary fit between external viral proteins and
host cell surface proteins
•
Some have a Broad host range
 Swine flu and rabies viruses
•
Some have a narrow host range
 Single tissue in a single species
•
e.g. Adenovirus, HIV
•
Phages of E. coli
Viral Reproduction
Simplified DNA Virus Life Cycle
• E.g. smallpox, herpes, chickenpox
• “Lock and Key” fit between viral
surface proteins and host cell receptors
initiates endocytosis
Electron micrograph of Bacteriophage T4
Bacteriophages are viruses that infects bacteria
Bacteriophage Reproduction
Bacteriophages (Bacterial Viruses)
•
Best understood of all viruses
•
Responsible for many advances in molecular biology
 Hershey-Chase expmts that showed that DNA is the
genetic material
 Restriction Enzymes used in Genetic Engineering
come from bacteria
Lytic Cycle of Bacteriophage T4
•
T4 is a Virulent Phage
•
Lyses host  death of host cell
The lytic cycle of phage T4
Lytic and Lysogenic reproductive cycles of phage , a temperate phage
What is the adaptive value of forming a prophage?
Lytic
Lysogenic
Cycle
Cycle
Prophage
The reproductive cycle of
an enveloped Virus
RNA viruses
• RNA serves as template to produce mRNA
 e.g. viruses that cause rabies, measles,
mumps, flu
DNA viruses
• DNA serves as template to produce mRNA
 Herpes (Cold sores, genital herpes)
 Smallpox
 Adenovirus
AIDS: Acquired Immunodeficiency Syndrome
• AIDS—caused by HIV
infection
• HIV = Human
Immunodeficiency Virus
HIV infecting a Helper T-Cell
HIV infection
AIDS around the world
(Source: UNAIDS)
Part of the World
People with HIV
New HIV
cases in
2002
North America
980,000
45,000
15,000
10,000
Sub-Saharan
Africa
South &
Southeast Asia
29.4m
3.5m
2.4m
2.8m
6m
700,000
440,000
240,000
India: 3.9 m
1.5m
150,000
60,000
45,000
East Asia &
Pacific
1.2m
270,000
45,000
4,000
Caribbean
440,000
60,000
42,000
20,000
Latin America
Deaths from
Aids in 2002
Children (under 15)
with Aids by end of
2002
The Structure of HIV: A Retrovirus (RNA virus)
Envelope protein
Carbohydrate
Lipid envelope
Reverse
Transcriptase
Protein
Capsid made of
protein
RNA
(2 copies of its genome)
Animation of HIV Life Cycle
Questions to Address:
1. Why does HIV infect a specific cell type,
T-helper cells (CD-4 cells)?
2. What is HIV’s Genetic material?
3. What are the roles of Reverse Transcriptase,
integrase, and protease?
4. How can knowledge of HIV’s life cycle be used to
develop anti-HIV treatments?
5. Reverse Transcriptase does not “proof read” like
DNA polymerase does.
a. What are the consequences?
b. Of what adaptive value is this?
HIV primarily infects T-Helper Cells!
• Why does HIV have a narrow host range?
• Why does the virus that causes rabies have a broad host range?
HIV
1.) Binding
2.) Fusion
3.) Infection
Envelope
protein
Capsid
CD4
Receptor
protein
Plasma membrane of
T-helper cell
RNA
Helper protein
Cytoplasm of white blood cell
(T-Helper Cell)
Overview of HIV’s Reproductive Cycle
Reverse
transcriptase
Viral RNA
DNA
strand
Doublestranded
DNA
1
DNA of host cell
Nucleus
Provirus
DNA
What’s happening?
1.
2.
2
3
4
3.
5
4.
Viral
RNA and
proteins
Cytoplasm
6
5.
6.
Reproductive Cycle of HIV—the details!
HIV
Entry
Reverse transcriptase
Viral RNA
Integrase
Viral RNA
Synthesis
of HIV proteins
HIV envelope proteins
come to cell surface
HIV assembles
and buds from
cell
Viral RNA
copied
to viral DNA
Viral DNA
integrates into
cell chromosomes
and makes more
viral RNA
Protease cleaves large
proteins into smaller ones
Treatments for HIV
1. Vaccines have been unsuccessful—why?
2. Reverse Transcriptase Inhibitors  Block viral DNA
formation from viral RNA
3. DNA base analogs  Block DNA elongation
•
e.g. AZT, 3TC (3-thiocytosine)
4. Protease Inhibitors  Block enzymes that process envelope
proteins
5. Why use a “Shotgun” approach?
6. Possible future treatments:
•
Plug drugs—drugs that plug receptors for HIV on surface of
host cell
•
Vaccines
Evolutionary Origin of Viruses
Evolved from fragments of Cellular Nucleic Acids
Evidence
1.
Viral genetic material similar to host cells genetic material
 Some viral genes are identical to host’s genes
2.
Eukaryotic viral genetic material is quite different to prokaryotic and
phage genetic material
3.
Eukaryotic viral genetic material is similar to transposons (“jumping
genes”)
 Transposons: highly mobile eukaryotic genetic material
4.
Phage DNA is similar to Plasmid DNA
 Plasmid DNA: highly “mobile” extra-chromosomal circular DNA
found in bacteria
Lysogenic Conversion
Lysogenic Conversion
Expression of prophage genes to produce toxins
1. Botulism
Bacterium  neurotoxin (coded by prophage)  paralysis  death
•
Are antibiotics effective against botulism poisoning?
2. Scarlet Fever
Bacterium  toxin (coded by prophage)  sore throat, strawberry-colored
tongue, rash  death
•
Give antibiotics within 3 days