Weird Life: Viruses and Prions
January 26, 2004

Readings: (Don't forget This Week's WarmUp and Good For)

Viruses are non-cellular infectious particles that consist of a genome (DNA or a related molecule RNA) wrapped in a protein coat or shell. Occasionally, viruses are surrounded by an envelope that consists of a piece of the the plasma membrane of the host cell that the virus picked up on its way out of a host cell.

Since viruses are cannot grow or replicate on their own, they are considered to be obligate intracellular parasites and generally not considered to be alive; but it is important to note that viruses have both living as well as non-living characteristics (a definition from one of the major textbooks in Biology). [Image of SARS virus]

Viral Diseases:

Viruses cause disease when they enter cells and 'hijack' the cell's own protein-making machinery, causing the cells to STOP production of normal cellular proteins, and START making viral proteins and copying viral DNA or RNA. Once the cell makes enough of the viral proteins and DNA, the cell even assembles these parts to make complete viruses in cells! At this point, when there are up to a few hundred mature viruses in the cell, the virus often bursts out of the cell, causing destruction of that cell, and an avenue of escape to spread to neighboring cells. Some viruses (like the Herpes viruses) also have the ability to insert their DNA into the DNA of their host, and exist as a "latent" virus until environmental conditions are right for the virus to exit cells.

There is an IMPRESSIVE array of viruses on Earth - even bacteria become infected with their own viruses! This is a great website for all kinds of cool electron microscope pictures of viruses, and lots of information on how viruses are classified and grouped: The Big Picture Book of Viruses. The main classification of viruses is usually based on what type of genetic material they carry into cells:

DNA viruses: These viruses carry their DNA into cells, and uses the cell's machinery to make viral proteins.

RNA viruses: These viruses carry RNA into cells, which is copied into DNA by an enzyme called reverse transcriptase and then made into viral proteins.

Viral Diseases of humans from A (adenovirus) -Z (varicella zoster)!! They're all here...!

A few notable pandemic viral diseases:

Influenza viruses - the subject of our first Good For!  CL

The AIDS pandemic: AIDS, first described in the late 1970s, has killed more than 22 million worldwide in the last 20 years. Nearly 40 million people world wide are infected by the virus, and currently, over 1 million people die every year.

See the CDC for information on West Nile Virus, SARS, smallpox, and other viral diseases...

5 January 2004: SARS returns to southern China. "The World Health Organization (WHO) has confirmed a new case of SARS (Severe Acute Respiratory Syndrome) in China. Chinese authorities announced plans to slaughter thousands of civet cats, ferret-like animals that are a delicacy in China's food markets and are suspected of transmitting the SARS coronavirus to humans." The SARS virus is an unusual entirely new virus related to the common cold virus that is part-animal and part-bird virus in origin. In the last 2 years, SARS has infected over 3,000 people in over 30 countries and has killed over 700 people by causing a severe pneumonia-like infection. [Image]

Prions: a newly discovered infectious agent

What are Prions? The term prion was coined by Dr. Stanley Prusiner to describe a "proteinaceous infectious particle". Dr. Prusiner started studying these proteins in 1972 after one of his patients died of Creutzfeld-Jacob Disease (CJD), a rare, fatal brain disease that occurs spontaneously in a few people per year.

Dr. Prusiner found two interesting things:
(1) CJD was very similar to a number of known brain disorders in animals called spongiform encephalopathies ('spongy brain' diseases), like scrapie - described below.
(2) CJD, as well as other spongiform encephalopathies, appeared to be spread in an unusual way - by abnormal proteins transmitted from organism to organism. These abnormal, infectious proteins - prions - have the ability to cause a mis-folding of a normal protein counterpart in brains.

The Prion (or "Protein only") hypothesis:

'Benign' (normal) PrP-c + the infectious 'scrapie form', PrP-sc ====> conversion of PrP-c to PrP-sc ====> spongiform encephalopathy

Prions are definitely infectious: when brain tissue from scrapie sheep is used to isolate the PrP-sc protein, and PrP-sc is injected into healthy animals, spongiform encephalopathy eventually results.

In October, 1997, Stanley Prusiner was awarded the Nobel Prize in Medicine "for his identification and characterization of the Prion and the association of this protein with neurological disorders." Press Release

Prion disorders of non-human animals:

Prion disorders of humans (there are others, but these are the main ones):

Mad Cow disease in England - 1986 and on

BSE first appeared in England in 1986, and scientists soon after realized that the disease BSE was strikingly similar to scrapie in sheep - the brains of BSE cattle clearly had spongiform encephalopathy.

How were the cows infected with BSE? Cattle with BSE had been fed a protein-rich feed made from the carcasses, bone meal, and the offal - slaughterhouse remains - of slaughtered sheep. This practice, common in modern factory farms, seems 'efficient' in that it makes use of carcasses as well as provides a protein-rich feed to encourage rapid growth of cows, BUT, it also provides an easy way for a prion to cross the species barrier from sheep into cattle, and then from cattle into the humans who eat beef. Scientists have evidence that the first cases of BSE were likely due to cattle being fed high-protein supplements from sheep infected with scrapie. [Image]

How humans were infected: In 1986, Government ministers in England reassured the public that beef was safe to eat. However, in the early 1990s, about 20 people in England were diagnosed with a new spongiform encephalopathy - called variant Creutzfeld-Jacob disease (vCJD), making health authorities suspicious that BSE had perhaps been transmitted to humans from BSE-infected cows slaughtered for human consumption. Tests indicated that this strain of CJD came from eating BSE-infected beef. Millions of cattle suspected of being infected with BSE in England and Europe were incinerated, but not before millions of hamburgers were, in fact, made from BSE-tainted beef. The beef industry in England still continues to suffer today. Currently over 110 people in Europe have contracted vCJD from BSE-tainted beef.

BSE in the USA: (From CBS's Mad Cow Disease interactive)
In the US, safety of meat is monitored by the USDA, who has set up a special website to track BSE in the US.
They also have a site on Actions to Prevent Bovine Spongiform Encephalopathy (BSE)

Fortunately, the risk of developing a TSE from eating BSE-tainted beef is very low. While between one and two million European BSE cattle were eaten by humans from the 1980s on, a relatively small number of people - 110 people at last count - are believed to have been infected with vCJD due to eating BSE-tainted beef. (It is still NOT known how many people will eventually become infected, though).

Unfortunately, there are no obvious symptoms of TSEs until the animal is in the advanced stages on the disease. The US 'Mad Cow' was a 6-year old dairy cow, and she had lived long enough to show symptoms of BSE. However, most cows are killed before they turn 2 years old, many years before they might show symptoms of BSE. The USDA currently tests only about 20,000 of the 40 MILLION cows slaughtered annually; this may have to increase if we want to assure safety as well as please our major beef exporters like Japan.

About time, or what!?! 'Downer' Cows Banned As Food. (12/ 30/ 03) Over 130,000 downer cows enter the human food supply every year, and only 1 in 5 is tested for BSE. Why are downer cows in the food supply anyway? Could politics have anything to do with it? Hmmmmm....

A new role for Prions: 12/26/03:
A normal role for prion proteins in the brain - human memory! WAY COOL!!! Scientists at the Whitehead Institute have recently found that the normal prion protein may be a 'storage device' for human memory. Prion-like proteins would be perfect for switching into different states to 'hold' memories for long periods of time. Stay tuned!

Optional: Do you really want to know? NOT for the squeamish... Grab a Boca burger and read on!
What is rendering? by Griffin Industries. More than 150 million pounds of waste animals by-products are discarded daily. Here's one company that makes the best of these useful by-products. Bonus:... free pick-up!
Advanced Meat Recovery: A technology for removing the last bits of meat from those ol' cow bones. Hold the sausages, please.....
What's really in pet food? You may never buy L'il Friskies again....
Dairy cows, hamburgers, and the Inefficient Efficiencies of Modern Farming; the sad and strange life of a modern Holstein milk cow. Originally from the New York Times, January 5, 2004

1. Describe ways in which viruses share characteristics of living cells.
2. How do viruses replicate? What is meant by the term 'obligate intracellular parasite'?
3. Compare and contrast DNA and RNA viruses - and give 2 examples of each.
4. Describe how the HIV virus causes the destruction of immune cells. How many people worldwide, and in the US, are infected with HIV?
5. What are prions and how do they cause brain diseases? What is a spongiform encephalopathy?
6. How are scrapie, mad cow disease, and vCJD related?
7. What might be the normal function of prion proteins?