Transcript Viruses

Viruses
Virus Unit
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Viruses
Prions
Viroids
Virusoids
Definition of Virus (Poison)
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Sub-microscopic
Intracellular
Parasitic
Do Not Grow &
Mature
• Do Not Reproduce
• Do Replicate
• Require a Host
Hieroglyph in Egypt 1400 B.C.
Possibly first written
record of a viral
infection 1400 BC.
Temple Priest
Siptah shows signs
of Paralytic
Poliomyelitis
Pharaoh Ramses V – 1196 B.C.
Believed to have died
due to smallpox.
Pustular lesions were
found on the face and
body of the mummy.
Smallpox was
Endemic in
China
by 1000 B.C.
Developed
Technique of
Variolation
1796 Edward Jenner -- Vaccination
Identification
of First Virus
1892 Dmitri Iwanowski (Plant Virus)
• Presented a paper to the St.
Petersburg Academy of Science
• Showed that extracts from
diseased tobacco plants could
transmit disease to other plants
after passage through ceramic
filters.
1898 Freidrich Loeffler and
Paul Frosch (Animal Virus)
Animal viruses
were soon
discovered via the
isolation of the virus
responsible for a
disease of cattle,
foot and mouth
disease, in 1898.
Foot and Mouth Disease
• FMD is a highly contagious and economically
devastating disease of cattle and swine.
• It also affects sheep, goats, deer, and other clovenhoofed (split-toed) ruminants.
• Many affected animals recover, but the disease
leaves them debilitated.
FMD causes severe
losses in the production
of meat and milk.
Because it spreads
widely and rapidly and
because it has grave
economic as well as
physical
consequences, FMD is
one of the most
dreaded animal
diseases for livestock
owners.
• Livestock producers
need to watch their
livestock for blisters
around the mouth or
muzzle, excessive
drooling, lameness,
and other signs of
FMD in their herd.
• Swine and cattle
typically show signs
of the disease within
two to seven days of
exposure.
Intact and ruptured vesicles on the tongue
of a cow.
Destroying a herd due to the finding of Hoof and Mouth Disease.
Despite the Fact that Viruses Were
Shown to Infect Plants and
Animals, there was Resistance to
the Idea that they could also Infect
Humans.
Polio was the First Human Disease
Recognized as having a Viral Cause.
Landsteiner and Popper in 1909
(Human Virus)
The discovery of the
first human virus
(poliomyelitis)
followed in 1900 with
the isolation of the
yellow fever virus.
• But it was not until the 1930's, however,
that it was possible to first get a glimpse of
the elusive viruses, for they are far too
small to be seen under a conventional
microscope - most viruses are in fact
smaller than the wavelength of visible
light.
Frederick Twort and Feliz d’Herelle
1915-1917 (First Bacteria Virus)
First individuals to
recognize that viruses
could infect bacteria.
They called these
agents
bacteriophages
(eaters of bacteria)
Bacteriophages are
the easiest viruses
to grow.
Spanish American War / Panama
Canal / Walter Reed/ Yellow Fever
• Yellow fever was first reported in Cuba in
1649, when one-third of Havana residents
died from the disease.
• From 1856 to 1879 (23 Years), the
disease struck the city nearly every month.
• Foreign occupiers were particularly
susceptible
Yellow fever had
been such a
formidable
enemy that it
had its own
nickname,
"Yellow Jack".
• U.S. officials were aware of the dangers
from disease going into the Spanish
American War.
• Despite knowing
that yellow fever
was most likely to
strike in the
summer rainy
season, the U.S.
invaded Cuba on
June 22, when the
Fifth Army Corps
landed at Daiquiri
during the Spanish
American War.
• "If we are kept here it will in all human
possibility mean an appalling disaster,
for the surgeons here estimate that
over half the army, if kept here during
the sickly season, will die.“
Letter from Lt. Col. Theodore Roosevelt to Secretary of War Russell Alger
• Fewer than 400 American soldiers were
killed in combat during the war. But more
than 2,000 contracted yellow fever during
the campaign.
Building the Panama Canal
Early History
• After realizing the riches of Peru, Ecuador,
and Asia, and counting the time it took the
gold to reach the ports of Spain, it was
suggested c.1524 to Charles V, that by
cutting out a piece of land somewhere in
Panama, the trips would be made shorter
and the risk of taking the treasures
through the isthmus would justify such an
enterprise.
• A survey of the isthmus was ordered and
subsequently a working plan for a canal was
drawn up in 1529.
• The wars in Europe and the thirsts for the
control of kingdoms in the Mediterranean Sea
simply put the project on permanent hold.
Finally in 1819 the Spanish government formally authorized
the construction of a canal and the creation of a company
to build it. The discovery of gold in California in 1848 and
the rush of would-be miners stimulated Americas interest in
digging the canal.
Time and mileage would be dramatically reduced when traveling from the
Atlantic to the Pacific ocean or vice versa. For example, it would save a
total of 18,000 miles on a trip from New York to San Francisco.
In 1876 an
international company
was organized; two
years later it obtained
a concession from the
Colombian government
to dig a canal across
the isthmus.
Caribbean workers arriving in
Panama, on board the 'Cristobal'
The international
company failed, and
in 1880 a French
company was
organized by
Ferdinand Marie de
Lesseps, the builder of
the Suez Canal.
• In 1904, the United States took on the task
of building the Panama Canal, after the
French company that started the project
gave up, having lost thousands of workers
to malaria and yellow fever.
Death and the Panama Canal
The death rate was so high that there was a
weekly worker turnover rate of 90%.
The Death Rate was so High, They
Ran Out of Places to Put the
Bodies
Yellow Fever Was an Unknown
Disease. How Was It Spread?
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Contaminated Clothing
Sneezing / Coughing
Direct Contact
Air
Water
Vector
• "Those three men opened the tightly-nailed, suspiciouslooking boxes. They opened those boxes inside that
house, in air already too sticky for proper breathing.
Phew! There were cursings, there were holdings of
noses. But they went on opening those boxes, and out of
them Cooke and Folk and Jernegan took pillows, soiled
with the black vomit of men dead of yellow fever; out of
them they took sheets and blankets, dirty with the
discharges of dying men past helping themselves. They
beat those pillows and shook those sheets and blankets
- "you must see the yellow fever poison is well spread
around that room!" Walter Reed had told them. Then
Cooke and Folk and Jernegan made up their little army
cots with those pillows and blankets and sheets. They
undressed. They lay down on those filthy beds. They
tried to sleep - in that room fouler than the dankest of
mediaeval dungeons! And Walter Reed and James
Carroll guarded that little house, tenderly, to see no
mosquito got into it."
"Microbe Hunters" by Paul De Kruif
Dr. Reed’s bold experiments proved
that yellow fever was indeed spread
by the bite of the mosquito Aëdes
aegypti.
• As a result of his discovery, yellow fever patients
were kept in rooms with mosquito screens, and
any nearby wet breeding grounds of the insect
were destroyed.
• The jungle was cleared back further than a
mosquito could fly.
• Within three months, yellow fever was
eliminated from Havana, for the first time in
over 150 years!
• Similarly, the same techniques were used in
Panama, which had suffered regular and
devastating yellow fever epidemics.
Brazil Flies Out Yellow Fever
Vaccine to Paraguay February 2008
• 50,000 doses of yellow fever vaccine were
distributed to Paraguay following the first
outbreak of the disease in the country for
34 years.
Max Theiler / Attenuated Vaccine
Walter Reed’s work allowed
Max Theiler to propagate
the virus in chick embryos
and successfully produce an
attenuated vaccine.
Attenuated vaccines are still
in use today.
Attenuated Vaccine
• These vaccines contain live microorganisms that have been cultivated under
conditions that disable their virulent
properties or which use closely-related but
less dangerous organisms to produce a
broad immune response.
Where Do Viruses Originate?
• The true ancestry of viruses is a mystery,
and perhaps always will be, for viruses
have left no fossil record behind them.
• They are so small that it is unlikely that
any record of them has survived for very
long, and they have only been known to
science for about a hundred years scarcely long enough to learn very much
about their evolution.
Evolved From Cells
• Some scientists believe that viruses
evolved out of cells, gradually losing so
much of their genetic information that they
became dependent on other cells for their
reproduction, or alternatively that they
arose from bits of genetic material within
the cell that acquired a life of their own.
Evolved With Cells
• Other scientists believe that viruses
originated and evolved along with the most
primitive forms of life, the simple
molecules that gained self-replicating
abilities.
• Some of these took the form of cells others evolved into the viruses which
parasitized those same cells.
Alien Theory
• Some scientists
propose that viruses
are so different from
anything on our
planet that they
must have found
their way here from
outer space hitching
a ride on a space
rock.
• Viruses are
Everywhere
• Viruses Confuse Us
• Viruses can
Crystallize (1935)
• Only One Nucleic Acid is Present
- DNA or RNA
• Protein Coat
- Capsomeres (individual
units) and Capsid (entire
protein coat)
• Naked / Envelope
- Naked / Only a Protein
Capsid
- Envelope / Lipid Membrane
• One or More Protein Types
- Serve for Attachment or as
a Docking Protein
- Attachment Proteins are
Called Spikes / Velcro
Viral
Composition
Host Range is the spectrum of host
cells in which a virus can replicate
• Without a host cell, viruses cannot carry out
their life-sustaining functions or reproduce.
• They cannot synthesize proteins, because
they lack ribosomes and must use the
ribosomes of their host cells to translate
viral messenger RNA into viral proteins.
• Viruses cannot generate or store energy in
the form of adenosine triphosphate (ATP),
but have to derive their energy, and all
other metabolic functions, from the host
cell.
• They also parasitize the cell for basic
building materials, such as amino acids,
nucleotides, and lipids (fats).
All Viruses Have a Limited Host Range
• Influenza
(Ducks, Chickens, Wild
Birds, Pigs, Humans)
• Smallpox and AIDS
(Attack only Man)
• Common Cold
(Specific for Cells in the
Upper Respiratory Tract)
Basic Principle of Viral Infection
• Even within a host they
attach to and invade only
those cells with the
appropriate receptor sites.
• If a cell’s outer surface
contains the receptor to
which a viruses’
attachment protein can
bind, the virus will be able
to invade and grow in that
cell.
Life Cycle of a Virus
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Adsorption or Docking
Penetration
Biosynthesis
Assembly and Maturation
Release
The entire process may take only 20-40 minutes and produce 50-200 new
viruses, each of which may do the same thing to a new cell.
Every Virus Has Two Life Stages
1. Viron Stage
- Dormant, Particulate, Transmissible
- Metabolically Inert
- “A piece of bad news wrapped in a
protein coat”
2. Infectious Stage
- Active, Intracellular
- Performs Life Processes
Lytic Pathway
• The virus interferes with the cell’s normal
metabolism, causing the symptoms associated
with the disease.
Latent or Lysogenic or
Temperate Pathway
• Cells remain infected, but the host is
symptom free.
• The host serves as a carrier of the disease
and is thus constantly spreading it.
Viral Diseases
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Polio
Influenza
Measles
Rubella
Roseola
Chickenpox
Common Cold
Lassa Fever
• Herpes
• HIV and AIDS
• Dengue
Hemorrhagic Fever
• Ebola
Hemorrhagic Fever
• Oncogenic Viruses
Definition Oncogenic Virus
• A virus capable of inducing the formation of
tumors (uncontrollable growth of cells).
• Also called tumor virus.
• A virus that transforms the infected cells so
that they undergo uncontrolled proliferation.
High Fructose Corn Syrup
• HFCS has already been linked to obesity
and diabetes.
• Cancer cells use fructose to fuel the
growth of tumors. (Pancreatic Cancer)
• Between 1970 and 1990, HFCS
consumption has increased by 1,000
percent
Oncogenic Viruses
1. Human Leukemia and Lymphoma
2. Hodgkin’s Disease
3. Kaposi’s Sarcoma
Leukemia
• Cancer of the blood or blood-forming organs.
People with leukemia often have a noticeable
increase in white blood cells (leukocytes).
Lymphoma
• Lymphoma is a form
of cancer that affects
the lymph nodes of the
body.
• The lymph nodes are
small, bean-shaped
organs located
underneath the skin in
the neck, underarm,
chest, abdomen, and
groin.
Hodgkin’s Disease
• Hodgkin's disease, (also called Hodgkin's
lymphoma), is a cancer that originates from
white blood cells called lymphocytes and spreds
from one lymph node group to another.
• When Hodgkins cells are examined
microscopically, multinucleated Reed-Sternberg
cells are the characteristic histopathologic
finding.
Kaposi’s Sarcoma
• Kaposi's sarcoma is a form of cancer that
affects areas such as bone, fat, cartilage,
blood vessels or other tissues.
The malignancy
results in purplish
grape-like lesions in
the skin,
gastrointestinal tract
and other organs.
A once-rare malignancy of the blood vessels Kaposi's sarcoma
is now associated with AIDS. It is more frequently associated
with AIDS in homosexual men than AIDS in IV drug users.
Viral Vaccines in General Use
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Influenza
Measles
Mumps
Polio
Rabies
Rubella
Hepatitis A and B
Varicella (Chickenpox)
Yellow Fever
Prions
• Infectious Protein Particles that are viral in
form and are composed completely of
protein with no nucleic acid present
1. Scrapi
2. Mad Cow Disease
3. KURU
4. Creutzfeldt-Jakob Disease
5. Chronic Wasting Disease
Scrapi
A fatal disease of sheep characterized by chronic itching and
loss of muscular control and progressive degeneration of the
central nervous system.
Note area where wool has been “scraped” away from constant rubbing.
• The name is derived from one of the
symptoms of the condition, wherein flocks
of affected animals will compulsively
scrape off their hides against rocks or
trees. The disease apparently causes an
uncontrollable itching sensation in the
animals. Other symptoms include
excessive lip-smacking, strange gaits,
and convulsive collapse.
Picture of Sheep from the rear shows bare patches from rubbing.
• The similarity of scrapie
to bovine spongiform
encephalopathy (BSE)
disease in cattle, with the
possibility of subsequent
transmission to humans,
has caused the Food and
Drug Administration to
propose regulations to
prohibit using sheep and
goat by-products as a
component in cattle
feeds.
Mad Cow Disease
Mad Cow Disease is the
common term for Bovine
Spongiform
Encephalopathy (BSE), a
progressive neurological
disorder of cattle which
can be transmitted to
other species, including
humans.
In humans, it is called
Creutzfeldt-Jakob
Disease, after the two
doctors who first
described the symptoms
of the disease.
The disease in cattle is called Bovine
Spongiform Encephalopathy (BSE) because
this form of the disease occurs in cows
(therefore, the term bovine), it causes a
sponge-like destruction of the brain
(therefore, the term spongiform
encephalopathy - enceph means brain and
pathy means pathology - meaning an
abnormality).
• BSE has a long incubation period, about 4
years, usually affecting adult cattle at a peak
age onset of four to five years, all breeds
being equally susceptible.
• In the United Kingdom (1986), the country
worst affected, 179,000 cattle were infected
and 4.4 million killed as a precaution.
• BSE was initially recognized in cattle in the
UK in 1986.
• The bovine agent reportedly had
originated from the scrapie agent, which
had been present in sheep in the United
Kingdom for at least 200 years.
• By 1993 more than 1,000 cases per week
were being reported.
• It is presumed, but will likely never be
proven, that the scrapie agent jumped
species and moved into cattle when sheep
offal (the leftover parts of butchered
animals) was included in protein
supplements fed to cattle.
After cattle started
to die, cattle
carcasses and
offal were included
in the same
protein
supplements -this seems to have
amplified the
epidemic.
Food Chain
Downed Cow
Mad Cow
Disease
United States
2003-2004
First case in the
United States
reported 12-23-2003
from a herd of 4,000
dairy cows in
Mabton,
Washington, part of
Yakima County.
An employee of a McDonald’s in Seoul, South Korea, hangs a sign on
Sunday (4 days after announcement of U.S. having Mad Cow) saying the
restaurant uses only Australian beef, as fears grow about the one case of
mad cow disease found in the United States.
Indonesian authorities Monday, December 29th (5 days after
announcement) instructed retailers to withdraw U.S. beef
products from sale due to fears of mad cow disease. A food
inspection officer examines imported beef products in a
Jakarta supermarket.
Dec. 30: Agriculture Secretary Anne Veneman
announces a list of restrictions to improve the safety
of the U.S. beef supply.
New Rules and Regulations
• Prohibit using “downers” for food
• Require results for meat from a cow
being tested for BSE prior to putting that
meat into the food supply
• Ban use of air-injections systems
• Brains, spinal cords, eyes, etc. will be
classified as risk materials and be
banned from human food supply.
U.S.A. Beef Consumption
The average American
consumes 65 pounds of Beef
per year.
United States slaughters 36
million cattle per year.
Currently test 40,000 cattle per
year.
Do the Math! What percent of
cattle slaughtered is tested for
the sake of public health?
How Does USA Compare?
Country
1. France
2. Japan
3. USA
Source: New York Times 2/9/04
Slaughters
6 million cattle
1.3 million cattle
36 million cattle
Tests
50%
100%
0.1%
In Summary
• BSE incubation period of from
2-8 years (mean = 4 years)
• Currently there is no test to
detect the disease in live
animals
• Prions produce a progressive
debilitating neurological illness
that is always fatal.
• Autopsied brains are filled with
holes and “sponge-like”.
• Economic impact can be
devastating to a country.
• Current testing in the United
States is inadequate and the
public health is at risk.
Chronic Wasting Disease
• Chronic Wasting Disease (CWD) is a
transmissible neurological disease of deer
and elk that produces small lesions in
brains of infected animals.
• It is characterized by loss of body
condition, behavioral abnormalities and
death. CWD is classified as a
transmissible spongiform encephalopathy
(TSE), and is similar to mad cow disease
in cattle and scrapie in sheep.
Creutzfeldt-Jakob Disease
• Creutzfeldt-Jakob Disease ("CJD") is a rare,
fatal brain disorder, which causes a rapid,
progressive dementia and associated
neuromuscular disturbances.
• The disease is often referred to as a subacute
spongiform encephalopathy because it usually
produces microscopic holes, in neurons that
appear "sponge-like".
• The disease is named after Drs. Hans Gerhard
Creutzfeldt and Alfons Jakob, who documented
the first cases of this illness in the 1920’s.
• Scientists in France have stumbled across
evidence that one strain of scrapie causes the
same brain damage in mice as CJD.
"This means we cannot rule out that at least some
CJD may be caused by some strains of scrapie,"
says team member Jean-Philippe Deslys of the
French
Atomic Energy Commission's medical research
laboratory in Fontenay-aux-Roses, south-west of
Paris.
Dark green areas are countries that have confirmed
human cases of Creutzfeldt-Jakob disease and light
green are countries that have bovine spongiform
encephalopathy cases.
Kuru
• Kuru is a rare
and fatal brain
disorder that
occurred at
epidemic levels
during the
1950s-60s
among the Fore
people in the
highlands of
New Guinea.
• The disease was the result of the practice
of ritualistic cannibalism among the Fore,
in which relatives prepared and consumed
the tissues (including brain) of deceased
family members.
• Brain tissue from individuals with kuru was
highly infectious, and the disease was
transmitted either through eating or by
contact with open sores or wounds.
• Government discouragement of the practice
of cannibalism led to a continuing decline in
the disease, which has now mostly
disappeared.
In 1976 Carleton Gajdusek
became co-recipient of the Nobel
Prize in Medicine for his
"discoveries concerning new
mechanisms for the origin and
dissemination of infectious
diseases."
Viroids
• Viroids and virusoids are the smallest and
simplest form of all recognized viruses and
self-replicating molecules.
• Replicating in the nuclei of plant cells,
they often cause striking diseases in their
host plants.
Viroids
• Viral agents
composed of
naked RNA that
are only 300-400
nucleotides long
• Only appear to
cause plant
diseases.
Effect of viroid on leaf
Yellow vein-banding symptoms on grapevine
Bark scaling
Fruit distortion on eggplant
Chrysanthemum plants infected with CSVd, showing severe
(left) and mild (centre) stunting symptoms. The plants on the
right are uninfected.
(Picture courtesy of Dr Yukimasa Hirata, Plant Biocenter, The Federation of
Wakayama Prefectural Agricultural Cooperative Associations, Japan).
Virusoids
• Virusoids, like viroids, are small, circular
molecules of genetic material.
• Virusoids "infect" other viruses, using the
replication processes of the host virus to
replicate themselves instead.