Viruses: Viruses


Definition of Virus (Poison): Definition of Virus (Poison) Sub-microscopic Intracellular Parasitic No 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: Smallpox was Endemic in China by 1000 B.C. Developed Technique of Variolation


1796 Edward Jenner -- Vaccination: 1796 Edward Jenner -- Vaccination


Identification of First Virus: 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 Paul Frosch (Animal Virus): 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: 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 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.


Slide11: 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.


Slide12: Intact and ruptured vesicles on the tongue of a cow.


Slide15: 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.: 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): 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’Herelle1915-1917 (First Bacteria Virus): 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: Spanish American War / Panama Canal / Walter Reed/ Yellow Fever


Slide20: Building the Panama Canal


Slide21: Caribbean workers arriving in Panama, on board the 'Cristobal' 


Death and the Panama Canal: Death and the Panama Canal The death rate was so high that there was a weekly worker turnover rate of 90%.


Slide23: 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. Mosquitoes would suck infected blood from monkeys in the forest, fly to the dig zone, bite a worker, and pass on the infection. Can-do Americans contemplated their options. Get rid of the monkeys? Kill all the mosquitoes? Not likely. Finally, someone figured out that the mosquitoes could not fly more than a mile without eating. The forest was cut back a mile on each side of the canal. Malarial Disease declined drastically. Welcome to out-of-the-box thinking, but Yellow Fever was still a problem.


Yellow Fever Was an Unknown DiseaseHow Was It Spread?: Yellow Fever Was an Unknown Disease How Was It Spread? FROM INFECTED MATERIALS? Some volunteers slept for weeks in the blood-soaked, vomit-stained fecal-contaminated nightgowns of recently deceased disease victims. FROM INSECTS? Others allowed themselves to be bitten mercilessly by (uninfected) mosquitoes. Private John R. Kissinger and clerk John J. Moran, were asked why they were agreeing to such life-threatening experiments. They said "We volunteer solely for the cause of humanity and in the interest of science".


Slide25: "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


Slide26: In August, Reed was called back to Washington. In his absence, Carroll, Lazear, and Agaramonte pushed forward and bred mosquitoes from eggs given to them by Finlay. Without my knowledge, they allowed the mosquitoes to feed on patients with established cases of yellow fever, and then applied the insects to the skin of volunteers, including themselves. The results they obtained were confusing: some volunteers got yellow fever, but others did not. Neither Carroll, Lazear nor Agaramonte became infected. They still had still not proven that mosquitoes could spread the disease.


A Lucky Break: A Lucky Break James Carroll decided to feed an "old" mosquito some of his own blood. Three days later, Carroll was ill with the yellow fever. Jesse Lazear's notebook had noted that the insect had fed twelve days before on a yellow fever patient, who was then in his second day of disease. Then Lazear was working at the bedside of a yellow fever patient when he was bitten by a stray mosquito. Five days later, he developed yellow fever; on the seventh day of his illness, Jesse died.


They had not allowed for the incubation period of the disease. : They had not allowed for the incubation period of the disease. Dr. Reed’s bold experiments proved that yellow fever was indeed spread by the bite of the mosquito Aëdes aegypti. 


Slide29: Yellow fever had been such a formidable enemy that it had its own nickname, "Yellow Jack".


Slide30: Dr. Reed’s discovery had an immediate and powerful effect and has since rid much of the world of this horrible disease.  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.  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.


Max Theiler / Attenuated Vaccine: 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.


Where Do Viruses Come From?: Where Do Viruses Come From? 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: 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: 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: 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.


Slide36: Viruses Confuse Us Viruses are Everywhere Viruses can Crystallize (1935)


Viral Composition: Viral Composition 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: Host Range The spectrum of host cells in which a virus can replicate.


All Viruses Have a Limited Host Range: All Viruses Have a Limited Host Range Smallpox and AIDS (Attack only Man) Influenza (Ducks, Chickens, Wild Birds, Pigs, Humans) Common Cold (Specific for Upper Respiratory Tract)


Basic Principle of Viral Infection: 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: Life 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 Stages: Every Virus Has Two Life Stages Viron Stage - Dormant, Particulate, Transmissible - Metabolically Inert - “A piece of bad news wrapped in a protein coat” Infectious Stage - Active, Intracellular - Performs Life Processes


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


Latent or Lysogenic or Temperate Pathway: 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.


Prions: Prions Infectious Protein Particles that are viral in form and are composed completely of protein with no nucleic acid present 1. Scrapi 2. KURU 3. Mad Cow Disease 4. Creutzfeldt-Jakob Disease


Scrapi: Scrapi 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.


Slide47: 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.


Slide48: Picture of Sheep from the rear shows bare patches from rubbing.


Slide50: The similarity of scrapie to bovine spongiform encephalopathy (BSE) (mad cow) 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 Mad Cow Disease is the common term for Bovine Spongiform Encepholopathy (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.


Slide52: The disease in cattle is called Bovine Spongiform Encepholopathy 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 encepholopathy - enceph means brain and pathy means pathology - meaning an abnormality).


Slide54: Downed Cow


Slide55: Downed Cow


Mad Cow DiseaseUnited States 2003-2004: 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.


Slide57: 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.


Slide58: 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.


Slide59: 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: New Rules and Regulations Prohibit using “downers” for food Ban cattle brains, spinal cords, and lower intestines from food supply 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: U.S.A. Beef Consumption The average American consumes 65 pounds of Beef per year. United States slaughters 36 million cattle per year. Plans to increase BSE testing in 2004 by testing 40,000 cattle. Do the Math! What percent of cattle slaughtered will be tested for the sake of public health?


How Does USA Compare?: How Does USA Compare? Country Slaughters Tests France 6 million cattle 50% Japan 1.3 million cattle 100% USA 36 million cattle 0.1% Source: New York Times 2/9/04


Institute of Medicine Report 1998: Institute of Medicine Report 1998 “There is a link between the use of antibiotics in food animals, the development of resistant microbes, and the zoonotic spread of pathogens to humans.”


In Summary: In Summary BSE incubation period of from 2-8 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.


Creutzfeldt-Jakob Disease: 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.


Slide67: At age 47, a woman feeling depression sought professional help at Massachusetts General Hospital. She became hypoactive, noticed impairment of her recent memory, and had urinary incontinence. Within a few months she became dizzy and had an unstable gait. At this point a CAT scan of the brain showed slight cerebral and central atrophy; delusion began to set in. By age 50 the patient’s cranial-nerve functions were still normal, as well as motor power, sensation, and coordination. The next symptom to appear was the occurrence of inappropriate laughter, and her replies to questions became irrelevant and incorrect.


Slide68: Mild tremor was noted, although the cranial-nerve functions, strength, coordination, and sensation were still intact. At this time another CAT scan was performed, and the results were the same as the year before. Within a week after this scan, she was readmitted with shaking spells. There was a constant alteration between laughing and crying, but reflexes were still normal. By the age of 51 and a half years, her speech had deteriorated rapidly, and a new CAT scan showed marked cerebral and cerebellar atrophy. Gradual deterioration continued up until her death four months prior to her fifty-fourth birthday. Note: She suffered with this for 7 years.


Kuru: 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.


KURU: KURU


Viroids: 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: 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


Slide73: Yellow vein-banding symptoms on grapevine Fruit distortion on eggplant Bark scaling


Slide74: 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).


Virosoids: Virosoids 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.


Viral Diseases: Viral Diseases Polio Influenza Measles Rubella Roseola Chickenpox Common Cold Lassa Fever Herpes HIV and AIDS Dengue Hemorrhagic Fever Ebola Hemorrhagic Fever Oncogenic Viruses


Oncogenic Viruses: Oncogenic Viruses Epstein Barr Disease Hodgkins Disease Human Leukemia and Lymphoma Kaposi’s Sarcoma


Viral Vaccines in General Use: Viral Vaccines in General Use Influenza Measles Mumps Polio Rabies Rubella Hepatitis A and B Varicella (Chickenpox) Yellow Fever