I. VIRUSES
Viruses are the smallest of parasites. They are wholly dependent on bacteria, plant cells or animal cells for reproduction. Viruses are intracellular molecular particles, often described as 'not quite alive' when outside of their host cells. They have a central core of nucleic acid and an outer cover of protein and sometimes a lipid (fat) coating. The nucleic acid core (DNA or RNA) represents the basic infectious material that can, in many cases, penetrate cells and initiate infection.
Several hundred different viruses may infect humans. Many have been recognized only recently. Viruses that occur primarily in humans are spread chiefly by humans. They are found in every part of the world. Some viruses, such as chicken pox, are exclusively human diseases. Zoonotic viruses are passed from nature to humans.
Viruses tend to be limited to specific geographic areas and environments. Rabies is found in France, but not England. Some Britains opposed the building of the "chunnel' between Britain and France for fear of rabies crossing over from continental Europe
The frightening Ebola virus comes from Africa. Ebola reston, a close relative, comes from Asia, but it does not infect humans.
Two special properties of viruses should be noted here. Some are oncogenic: they can cause cancer. Examples are viruses implicated with certain lymphomas and leukemias. Some viruses confer lifetime immunity after a single bout of the disease. Others are capable of recurrence. Examples include chicken pox, discussed below, and the herpes simplex virus that we covered in a previous unit.
Viral diseases are not ordinarily susceptible to antibiotics. Acyclovir inhibits replication of the herpes virus. AZT and protease inhibitors can suppress the HIV virus down to undetectable levels, but doesn't remove the infection. Some viruses are notoriously lethal. Others produce a mild infection in children, but are fatal to adults. A few as mentioned above are hidden away in the body only to strike again when bodily resistance is reduced.
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II. THE ORIGINS OF VIRUSES
Until the moment that a virus enters a cell, it seems more dead than alive. At its core, a virus is pure genetic information--in a form compatible with the genetics of our own body. Our cells also contain vestiges of early life on earth in the form of ribosomal RNA. Why is this significant? Disease producing bacteria also contain ribosomal RNA.
It is unknown whether viruses originated as primitive self-replicating molecules that later began to parasitize living cells or if they began as genes that somehow became extracellular as 'renegade' DNA. (My note: recall that plasmids can function extracelluarly also. Some plant viruses such as tobacco mosaic are crystalline. Have you seen the classic film The Andromeda Strain? They are something like that.)
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III. CHICKEN POX (Called VARICELLA in textbooks)
This is an acute viral disease, usually of children. The epidemics occur in cycles as new groups of susceptible arise over time. Childhood chicken pox is usually benign; however, in adulthood it can be severe or fatal. There is now a vaccine. Chickenpox can sustain itself indefinitely among small populations of just a few thousand.
Chickenpox virus remains in the body after the acute phase is over. It reemerges decades later as shingles. When in recurrence as shingles, the virus can spread to infect children or others previously unexposed. One adult, therefore, can reintroduce chicken pox forty or more years after the last epidemic. It can therefore cross generations and sustain itself in populations of only a few thousand. How's that for effective strategy!
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IV. A BIOTECHNOLOGY PRIMER
(My note: This section is OPTIONAL!)
In 1973, two California geneticists, Cohen and Boyer, took a piece of DNA from an African clawed frog and spliced it into that of a common bacterium. They, and biologists world wide, realized that biotechnology had become practical. Cohen predicted that one day bacteria would produce human insulin. Indeed, Ely Lilly in Indianapolis does so today. Moving genes from one organism to another made it possible. Previously, insulin was extracted from beef animal organs.
How is it done? At the molecular level, genes (the units of heredity) are just pieces of DNA along the well-known double helix. Many proteins have medical and industrial importance, and with gene splicing, bacteria can be harnessed to make them.
The following section is technical. If you take it a step at a time, you can master it and have a basic idea of what gene splicing is when you hear about it on the news. Before beginning, consider this: bacteria are infected by viruses, too. They have evolved defenses against viruses and have developed ways of identifying and removing viruses from their DNA.
What bacteria have done is this: they have evolved 'chemical scissors' to snip out invading viruses. Those chemical scissors are called enzymes. Over time, bacteria have developed an inventory of enzymes that can cut genes--or any part of a gene--from its DNA. Remember, viruses infect by inserting their own DNA. With their inventory of enzymes, the bacterium has a tool kit to snip out the undesired viral DNA.
So far, we have described a way to take genes out of a strand of DNA. How can DNA be inserted back into the bacterium?
You will recall our discussion of plasmids, the tiny rings of DNA floating freely in or outside of a bacterium. Using the same enzymes, the plasmid rings are opened and the genes are inserted. The plasmids are then reinserted into the bacteria, and voila! The bacterium functions with the foreign gene. Thus, 'recombinant DNA' is created.
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Genetically altered bacteria are then grown in nutrient broth where they can then produce a desired new protein--a process akin to making beer. Human growth hormone and insulin are made in this way. It is a stunning achievement.
There is an important implication we should also note here: The similarity of our DNA to that of other celled animals, bacteria, and the other forms of life suggest a common origin long, long ago.
What about plants? They are more challenging. They don't have plasmids. Scientists therefore remove the desired genes chemically, gold plate them, and 'fire' them at high velocity into the recipient cells. Some of the plant cells will take them into their chromosomes and the implanted genes are passed onto succeeding generations.
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V. VIRAL RESISTANCE AND ADAPTABILITY
Do you recall our discussion of plasmids and 'jumping genes'? They were a mechanism for DNA to move between not only various species of organisms, but between entire families of organisms. For example, they can move between bacteria and yeasts, between plants and bacteria, between complex parasites and their host cells. Some researchers suspect that HIV retrovirus had its beginning as such 'renegade' genetic material.
Some viruses are notoriously unstable. The flu virus is a dramatic example. Not only are they capable of spontaneous change, they are also capable of trading genes in a process called re assortment. This is why a different one emerges each year--and some years the new configuration is devastatingly virulent as in 1918.
Viruses are also capable of drug resistance similar to that found in bacteria after repeated exposure to antibiotics. Resistance by the herpes simplex virus to Acyclovir was observed early after introduction of the drug. It was seen most dramatically in AIDS patients with weakened immune systems.
The HIV virus, some estimate, is mutating at a rate of 1% a year. Not surprisingly, HIV resistance to the drug AZT emerged early on in many patients. The new three drug 'cocktails' with protease inhibitors are designed to thwart drug resistance for as long as possible. A similar strategy was used with the combination of drugs used to treat tuberculosis in the late 1940s.
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VI. EBOLA
The virus that causes Ebola is one of more than a dozen that researchers call "hot agents"--viruses that spread easily, kill swiftly, and have no cure or vaccines. They are considered so dangerous that workers in the field have developed their own dramatic terminology to describe them. The Hot Zone by Richard Preston became a best seller when it came out in 1994. Hollywood responded with its own fictionalized portrayal in Outbreak.
Ebola is a filovirus, literally a thread virus. The filoviruses include Marburg (named after a city in Germany), Ebola Sudan, Ebola Zaire, and Ebola Reston--a city in Virginia were an Ebola variant from Asia killed a monkey colony. Ebola reston does not infect humans.
Ebola was first documented in July, 1976 when it struck a small village in Sudan. Victims became fevered and began to bleed, much as they do with a better known "hot" viral disease, Lassa fever. Ebola killed half or more of the people it infected. In September it struck again in Zaire, seemingly more virulent than before. Sweeping through more than 50 villages, it killed 90% of its victims. In the virulent virus business, Ebola is called a 'slate-wiper' for its ability to decimate populations. To prevent an explosive epidemic in the capital city of Kinshasa, the Zairean government sealed off all roads into the afflicted area.
That epidemic drew little interest in this country apart from the experts in virology. The year 1976 was the nation's bicentenial celebration. An outbreak of respiratory illness among American Legionnaires in Philadelphia caught the media's attention instead of African Ebola.
The natural host for Ebola is unknown. When it reappeared in 1995 and killed at least 97 people, researchers were anxious to trace the virus to its source. This requires methodical field work, going door to door asking who has been sick and when they became sick. A series of contacts is established, hopefully leading to 'patient zero', the first one infected. The study of an Ebola epidemic is only an occasional opportunity. It is a bit like a comet in the sky: you can only study it when it arises.
Tropical regions may pose the greatest threat of unleashing viruses, simply because they contain such great concentrations of different species of plants and animals--and the viruses that prey on them. Tropical rain forests are ancient: 15 million years old in the Amazon; more than 100 million years old in Australia. Apart from the oceans, they are the deep reservoirs of life on this planet.
As human populations penetrate previously uninhabited regions, unknown viruses may be uncovered that have long remained sequestered away from people. An as yet unnamed virus related to distemper and measles briefly appeared in Australia last April. It infected 14 horses and one trainer. When a virus does emerge from its seclusion, air travel offers it transit anywhere in the world. In 1989, Ebola reston came to Reston, Virginia in a shipment of monkeys for research.
The animals began "dropping like flies," said one observer. Unlike the African Ebola, the reston variety became air born like the common cold, traveling everywhere in the building. The monkeys had come from the Philippines. The US Army did a full scale decontamination of the building. The Ebola killed monkeys, but didn't kill humans. The virus made a dramatic appearance-and disappeared.
Ebola is distantly related to measles, mumps, and rabies. It is a single strand of RNA and is considered to be extremely ancient. Then a "hot" virus multiplies in a host, it can saturate the body with virus particles. This unbridled growth is called "extreme amplification." It is as if the virus converts its host into itself.
After exposure to Ebola, headache begins by the 7th day. By the tenth day, there are nausea, fever and vomiting--black and red vomit. The eyes turn red, the skin yellow. There is then a massive hemorrhaging from every orifice in the body. The massive bleeding is described as 'crashed and bled out.' Many tissues and organs are virtually liquified.
Along the Ebola River, the villagers have an effective cultural adaptation to epidemic disease such as Ebola. It might be called 'reverse quarantine.' When a deadly disease strikes a village, no one enters and no one leaves until the disease has run its course. It is a very effective containment strategy.
..... CJ '99
Resources
Bishop, J. "How it works, A biotech Primer" Wall Street Journal. May 20, 1994.
"Enemy Within" Chicago Tribune. May 21, 1995.
Garrett, L. The Coming Plague. New York: Farrar, Straus and Giroux, 1994.
Larson, E. "The Flu Hunters" Time. February 23, 1998.
"Latest Ebola outbreak linked to chimpanzees" Chicago Tribune. February 16, 1996.
Griffiths et al An Introduction to Genetic Analysis. New York: W. H. Freeman, 1996.
Preston, R. The Hot Zone. New York: Random House, 1994.
Price, P. Biological. Fort Worth: Saunders/Harcourt, 1996. (The title is not a misprint.)
"Viruses" National Geographic. July, 1994, pp 58-91.
"Where Does Ebola Hide?" Time. March 4, 1996.
"Ebola virus hits monkeys in Texas" Chicago Tribune. April 16, 1996.