VirusesViruses

Virus UnitVirus Unit

• Viruses

• Prions

• Viroids

• Virusoids

Definition of Virus (Poison)Definition of Virus (Poison)

• Sub-microscopic• Intracellular• Parasitic• Do Not Grow &

Mature• Do Not Reproduce• Do Replicate• Require a Host

Hieroglyph in Egypt 1400 B.C.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.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 -- Vaccination1796 Edward Jenner -- Vaccination

Identification of First Virus

1892 Dmitri Iwanowski (Plant 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 1898 Freidrich Loeffler and Paul Frosch (Animal Virus)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 DiseaseFoot and Mouth Disease• FMD is a highly contagious and economically

devastating disease of cattle and swine. • It also affects sheep, goats, deer, and other cloven-

hoofed (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 1909Landsteiner and Popper in 1909(Human Virus)(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’HerelleFrederick Twort and Feliz d’Herelle1915-1917 (First Bacteria Virus)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 Spanish American War / Panama Canal / Walter Reed/ Yellow FeverCanal / 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 CanalBuilding the Panama Canal

Early HistoryEarly 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.

Caribbean workers arriving in Panama, on board the 'Cristobal' 

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.

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 CanalDeath 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 Yellow Fever Was an Unknown Disease. How Was It Spread?Disease. How Was It Spread?

• Contaminated Clothing

• Sneezing / Coughing

• Direct Contact

• Air

• Water

• Vector

• "Those three men opened the tightly-nailed, suspicious-looking 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 VaccineMax Theiler / Attenuated VaccineWalter 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 VaccineAttenuated Vaccine

• These vaccines contain live micro-organisms 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?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 CellsEvolved 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 CellsEvolved 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 TheoryAlien 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)

Viral Viral CompositionComposition• 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

Host Range is the spectrum of host Host Range is the spectrum of host cells in which a virus can replicatecells 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 RangeAll 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 InfectionBasic 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 VirusLife Cycle of a Virus• 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 StagesEvery 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 PathwayLytic Pathway

• The virus interferes with the cell’s normal metabolism, causing the symptoms associated with the disease.

Latent or Lysogenic or Latent or Lysogenic or Temperate PathwayTemperate 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 DiseasesViral Diseases

• Polio• Influenza• Measles• Rubella• Roseola• Chickenpox• Common Cold• Lassa Fever

• Herpes• HIV and AIDS• Dengue Hemorrhagic Fever• Ebola Hemorrhagic Fever• Oncogenic Viruses

Definition Oncogenic VirusDefinition 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 SyrupHigh 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 VirusesOncogenic Viruses

1. Human Leukemia and Lymphoma

2. Hodgkin’s Disease

3. Kaposi’s Sarcoma

LeukemiaLeukemia

• Cancer of the blood or blood-forming organs. People with leukemia often have a noticeable increase in white blood cells (leukocytes).

LymphomaLymphoma • 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 DiseaseHodgkin’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 SarcomaKaposi’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 UseViral Vaccines in General Use

• Influenza• Measles• Mumps• Polio• Rabies• Rubella• Hepatitis A and B• Varicella (Chickenpox)• Yellow Fever

PrionsPrions

• 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

ScrapiScrapi

Note area where wool has been “scraped” away from constant rubbing.

A fatal disease of sheep characterized by chronic itching and loss of muscular control and progressive degeneration of the

central nervous system.

• 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 DiseaseMad 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 Mad Cow DiseaseDisease

United States United States 2003-20042003-2004

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 RegulationsNew 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 ConsumptionU.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?How Does USA Compare?

Country Slaughters Tests

1. France 6 million cattle 50%

2. Japan 1.3 million cattle100%

3. USA 36 million cattle 0.1%

Source: New York Times 2/9/04

In SummaryIn 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 DiseaseChronic 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 DiseaseCreutzfeldt-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 FrenchAtomic 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.

KuruKuru

• 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."

ViroidsViroids

• 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.

ViroidsViroids

• 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

Fruit distortion on eggplant

Bark scaling

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).

VirusoidsVirusoids

• 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.