Viruses

The first virus to be discovered was the tobacco mosaic virus (TMV). In the 1880s, researchers figured out that tobacco plants could catch what appeared to be a contagious germ from other, infected tobacco plants. Subsequent researchers knew enough about bacteria to know how to search for a bacterial pathogen by filtering extracts through special filter paper, etc., but none of those methods worked to find the cause. Someone figured out that it wasnt just toxins produced by an infected plant, but that there was some agent that was reproducing, and that generation after generation, could still infect tobacco plants. Attempts to grow the pathogen on petri dishes were unsuccessful. Researchers were also puzzled by the fact that, unlike any bacteria (living cells) that were known, this pathogen could not be killed by alcohol, thus they were beginning to suspect some kind of chemical that could only reproduce when inside an appropriate host. Finally in the 1930s, TMV was found by crystalizing it! Indeed, it was a chemical that could reproduce like it was alive, yet needed the cells of a host organism to do so, and could be crystalized, but remained viable and infectious even then. The smallest viruses are smaller than ribosomes in cells, and the largest are so big that theyre just barely visible under the highest power of magnification possible with a regular light microscope. A single virus particle is called a virion, and is made of nucleic acid (either single or double-stranded RNA or DNA depending on what kind of virus it is) in a protein shell. The viral nucleic acid (RNA or DNA) is one molecule (one chromosome), consisting of from four to several thousand genes in length. Much current DNA technology research is aimed at inserting good genes into otherwise harmless viruses, then letting these infect animals / humans as a way of inserting the needed gene into the hosts cells. The surrounding protein coat that encloses the viral nucleic acid is called a capsid, and its shape, its protein structure, is specific to each kind (species?) of virus. An isolated virion is inert: it has no metabolic equipment, thus cannot do any chemical reactions on its own. Virions can be separated into separate nucleic acid and protein components, each separately crystallized and stored, and yet if mixed back together, can reassemble and be just as viable, as infective, as before. 1

Viruses are obligate intracellular parasites, that is, they can express their genes, do chemical synthesis of more viral nucleic acid and protein, and replicate only within a living cell of the correct host species. When a virus enters a host cell, it takes over the host cells metabolic machinery and chemical pathways and uses these to make more virus protein and nucleic acid, which then spontaneously come together to form not two, but MANY new virions. Viruses are capable of replicating many copies of them, which then go infect other cells. However, each type of virus has a limited range of host cells. For example, TMV wont infect humans, but because humans are closely related to gorillas, many human viruses can be transferred from humans to zoo gorillas and make them very sick (hence one of the reasons why people arent allowed to feed zoo animals). Viruses use a sort of chemical lock and key mechanism to join to receptor sites on the surface of their host cell, thus the host may be only one or or several closelyrelated species. Some viruses can insert themselves (their DNA) into their hosts genetic material, stay there, and replicate along with host DNA when the host cells do mitosis. Herpes viruses are especially known for this, and it is thought that some forms of cancer may be caused in this way. Bacterial viruses (viruses that infect bacteria yes, such things really do exist!) are known as bacteriophages. When these replicate, they then burst out of the host bacterium cell, killing it as many viruses are released. Many plant viruses are passed in the usual way by contamination from another infected plant (dont work in the garden when the leaves are wet), but some others are passed to the next generation in the seed. Many animal viruses have a slightly different way of entering or leaving their host cells: many have an external membrane cloaking device which is derived from the cell membranes of their host cells. This bit of borrowed cell membrane helps the virus to enter/leave a host cell unnoticed, and without exploding the host cell. To infect a new cell, the membrane surrounding the virus joins with the cell membrane of a host cell, and the capsid and nucleic acid sneak inside. When the new virions leave, each wraps a bit of cell membrane around itself on the way out.

Viruses like Rubella, Rabies, and HIV can also cross the placenta of an infected female mammal and infect her growing baby. If the baby lives, it may be deformed (Rubella) or be born with a viral infection (HIV and Rabies). Interestingly, because Rabies can be transferred transplacentally, many zoos will no longer accept donations of pet skunks because there is a question as to how many generations of captive-rearing with no signs of Rabies are necessary to insure that an animal is, indeed, free of Rabies. One of the biggest questions about viruses is, Are they alive? Consider that viruses

unlike living organisms, can be crystallized, then be put back together and be viable (this would kill a bacterium),

like living organisms, have genetic programming, can mutate, and can evolve (this is the reason we cant make an AIDS vaccine that will always work),

unlike living organisms, cannot reproduce independently, but like living organisms, can reproduce, and

eukaryotic virus genes are more similar to eukaryotic genes, and prokaryotic virus genes are more similar to prokaryotic genes, suggesting that viruses may have evolved from fragments of cellular nucleic acids that acquired special packaging.

Almost all known medicines, such as antibiotics, work by inhibiting some specifically bacterial chemical function, thereby killing the bacteria without harming our cells which dont do the targeted chemical reaction. Since viruses use our cells to do their work, there is really no antibiotic that can effectively inhibit their growth without messing up the workings of our cells. Thus, despite all the frantic AIDS research, there remains no known cure, no antiviral agent to zap viral infections. Antibiotics do NOT help, and may actually make matters worse. Because antibiotics kill the good bacteria in your system (even if bad bacteria are present), taking them can cause secondary fungus infections. Additionally, if some bad bacteria are present in your system, theres always the chance that there will be just that one mutant one with the chemical machinery to survive the antibiotic, and via natural selection, live to reproduce and pass on its resistant genes when all the others have died. 3

This is how multiple-antibiotic-resistant strains of bacteria develop (multiple-drugresistant Staphylococcus aureus staph infection has become such a bad problem in hospitals, etc. that medical people now refer to it by the nickname, M-D-R-S-A). Additionally, the more your body is exposed to antibiotics, the greater the chance that you might develop an allergy to one or more, and not be able to take it/them when you really need to. It does no good to take antibiotics for a cold (unless you count the money you just gave to the doctor and drug company as being to their benefit). The good news is that our immune systems can learn to fight off previouslyencountered viruses. The first time you are exposed to a virus, your immune system starts to make antibodies against it, so that next time you get an invasion of that virus, you can fight it off without getting sick. Some viruses, like those that cause colds and flu, mutate so quickly (we talk about various strains of flu virus) that they become so different from the last one to which you were exposed that you immune system doesnt have the right instructions to fight off the new variety. Some viruses, like small pox, mumps, and measles, mutate more slowly, so for these once someone gets the disease, his/her immune system can fight any future exposures and the person doesnt get sick again. For these viruses, any exposure to even a closely-related strain will trigger an immune reaction, hence vaccination, harmless variants/derivatives of pathogenic viruses, are effective in stimulating the immune system to learn how to fight future exposures. As you hopefully recall from our discussion of the immune system, one big problem with the AIDS virus is that it infects and destroys the cells of the immune system that are needed to create immunity to fight off any new pathogens. A person who has been exposed to the AIDS virus does make anti-AIDS antibodies (AIDS testing involves checking for the presence of anti-AIDS antibodies, not the actual virus, itself), but often cannot make antibodies against anything new, thus usually ends up dying of some secondary infection that his/her immune system couldnt fight.

MAIN VIRUSES AFFECTING HUMANS: influenza = flu (from the influence of the stars astrology): There are a number of strains and the virus mutates a lot. It infects the respiratory system, usually with fever (vomiting?). It has a 48-hr incubation after exposure. mumps: It infects the salivary (parotid) glands in the neck, also (especially in post-puberty patients) possibly other organs like testes, but usually doesnt cause sterility. It is most common in children, and spread by saliva. It is most common in late winter to spring. It often causes pain on chewing/swallowing, especially when swallowing acidic substances (pickles), which is one of the earliest symptoms. Then the person has a fever, too (the highest fever I can ever remember having as a child was with mumps). infectious mononucleosis = mono: This infects certain WBCs. The symptoms include sore throat and tiredness. Often there is involvement of lymph nodes and spleen, and care must be taken to not rupture an enlarged spleen (limit physical activity). This virus is closely-related to Herpes viruses, and like them, remains in cells DNA forever. Because of this, it can sometimes become active again, and the person may shed virus (in saliva) without even feeling bad or knowing it. In some people this may come back as Epstein-Barr virus (EBV) or chronic fatigue syndrome (there is some debate as to whether this virus or an as-yetundetected, closely-related virus is responsible for that). Mono is most common in teens and young adults. Virus is shed in the saliva both while the person is actively sick and intermittently throughout the rest of his/her life. The mono virus lives in and changes certain WBCs, and there is evidence that it may also be able to live in some mucous membrane cells in the nose/throat area. Interestingly, the WBCs it changes have a growth potential like malignant cells, but are normally kept in control by the immune system. In people with weakened immune systems, there are implications that EBV is associated with certain kinds of cancer. common cold = Rhinovirus (rhino = nose): There are a number of strains of this virus. It is more common in cold months. Symptoms usually do not include fever. Fatigue and/or stress can increase a persons susceptibility. 5

poliovirus causes poliomyelitis = polio (polio = gray; myelo = spinal cord; -itis = inflammation of): This is an infection of the CNS which can lead to paralysis. Back during WWII, people were put in iron lungs until they could start breathing on their own again. Some people had/have varying degrees of permanent damage from a small limp to needing a wheelchair. Were finding now that many people who recover fully are having some symptoms re-appear later in life: weakness in legs, etc. This disease was more common in warm months and in children, thus at one time, people believed polio was associated with consumption of too much ice cream! Polio is spread by saliva. measles = Rubeola (rubeo = red): This is common measles. Symptoms and signs include white spots on mucous membranes in the mouth, red spots/rash on the skin, and fever and cold symptoms. It is spread by saliva and nasal secretions. German measles = Rubella: If this infects a pregnant woman (or from vaccination of it), it can cross the placenta and cause birth defects (first trimester). The patient is infective from one week before onset of the rash until one week after it fades. The symptoms are often milder than regular measles. Herpes viruses (herpes = creeping)
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smallpox: This makes pus-filled pox. People who had the more mild cowpox didnt get this, which led to the development of vaccinations chickenpox: This stays in the persons DNA (hiding in certain nerve cells) and can come back as shingles, Herpes zoster or Varicella zoster. As shingles, this virus is in the CNS, follows a nerve, and thus, is painful. Chickenpox symptoms include mild headache, fever, and a rash consisting of raised pox filled with fluid. The lesions are no longer infective when crusted over cold sores: These stay in the persons DNA (hiding in mucous membrane around the lip area) and can come back during periods of stress. Herpes simplex type I is the responsible agent.

genital herpes: This is caused by Herpes simplex type II, and is spread by sexual contact.

hepatitis (hepato = liver): There are a number of different, related diseases which go by the name of hepatitis. human papiloma virus = HPV = genital warts This is another sexually-transmitted virus. Frequently a person develops several of these in close proximity. The warts begin as soft, moist, reddish swellings on either the external genital area or within the urethra (males) or vagina (females) and grow rapidly. At least one type inserts its DNA into the DNA of the host cells, and all are difficult to treat/control. Women who get this frequently end up with cervical cancer several years later, necessitating surgery to remove part or all of the uterus. rabies: May be found in some dogs and bats. It is also know as hydrophobia because the animal has trouble drinking, and so appears to be afraid of water. Rabies invades the CNS, leading to paralysis and death. The virus is present in the saliva of infected mammals, and is often transferred by a bite. In US, most cases are from the bites of wild animals since dogs are vaccinated. Beware of behavior changes in wild animals: skunks or other nocturnal animals active in daytime, or wild animals lacking normal fear of humans. Rabies is more likely from carnivores rabbits, etc. usually dont have rabies. Current treatment involves vaccines around the site of the bite and intramuscular. warts: These are contagious, and are most frequent in older children. Their appearance and size are influenced by location and degree of irritation (most frequent on sites subject to trauma like fingers, elbows, knees; plantar warts on soles of feet are flattened by pressure). Warts may persist by autoinoculation. Usually, complete regression in several months is common with or without treatment, but some may last for years. Most do not become malignant. AIDS = acquired immunodeficient syndrome = HIV = human immunodeficiency virus: AIDS is transferred in blood and other fluids. Tears during sexual contact (especially likely in anal sex because the rectum not designed for that) are often an entry point, as well as IV drug users sharing needles. As mentioned, AIDS infects/kills cells of the 7

immune system that help fight off other infections. Thus the person often dies from secondary infections. The AIDS virus contains RNA as its genetic material and an enzyme called reverse transcriptase. Because of this, the AIDS virus can do reverse transcription to go from its RNA to DNA, which is inserted into the persons cells to control replication of more virus.

carterjs@uc.edu ************

Virus Structure Viruses are not plants, animals, or bacteria, but they are the quintessential parasites of the living kingdoms. Although they may seem like living organisms because of their prodigious reproductive abilities, viruses are not living organisms in the strict sense of the word. 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). Although viruses have been speculated as being a form of protolife, their inability to survive without living organisms makes it highly unlikely that they preceded cellular life during the Earth's early evolution. Some scientists speculate that viruses started as rogue segments of genetic code that adapted to a parasitic existence. All viruses contain nucleic acid, either DNA or RNA (but not both), and a protein coat, which encases the nucleic acid. Some viruses are also enclosed by an envelope of fat and protein molecules. In its infective form, outside the cell, a virus particle is called a virion. Each virion contains at least one unique protein synthesized by specific genes in its nucleic acid. Viroids (meaning "viruslike") are disease-causing organisms that contain 8

only nucleic acid and have no structural proteins. Other viruslike particles called prions are composed primarily of a protein tightly integrated with a small nucleic acid molecule. Viruses are generally classified by the organisms they infect, animals, plants, or bacteria. Since viruses cannot penetrate plant cell walls, virtually all plant viruses are transmitted by insects or other organisms that feed on plants. Certain bacterial viruses, such as the T4 bacteriophage, have evolved an elaborate process of infection. The virus has a "tail" which it attaches to the bacterium surface by means of proteinaceous "pins." The tail contracts and the tail plug penetrates the cell wall and underlying membrane, injecting the viral nucleic acids into the cell. Viruses are further classified into families and genera based on three structural considerations: 1) the type and size of their nucleic acid, 2) the size and shape of the capsid, and 3) whether they have a lipid envelope surrounding the nucleocapsid (the capsid enclosed nucleic acid). There are predominantly two kinds of shapes found amongst viruses: rods, or filaments, and spheres. The rod shape is due to the linear array of the nucleic acid and the protein subunits making up the capsid. The sphere shape is actually a 20-sided polygon (icosahedron). The nature of viruses wasn't understood until the twentieth century, but their effects had been observed for centuries. British physician Edward Jenner even discovered the principle of inoculation in the late eighteenth century, after he observed that people who contracted the mild cowpox disease were generally immune to the deadlier smallpox disease. By the late nineteenth century, scientists knew that some agent was causing a disease of tobacco plants, but would not grow on an artificial medium (like bacteria) and was too small to be seen through a light microscope. Advances in live cell culture and microscopy in the twentieth century eventually allowed scientists to identify viruses. Advances in genetics dramatically improved the identification process.

Capsid - The capsid is the protein shell that encloses the nucleic acid; with its enclosed nucleic acid, it is called the nucleocapsid. This shell is composed of protein organized in subunits known as capsomers. They are closely associated with the nucleic acid and reflect its configuration, either a rod-shaped helix or a polygon-shaped sphere. The capsid has three functions: 1) it protects the nucleic 9

acid from digestion by enzymes, 2) contains special sites on its surface that allow the virion to attach to a host cell, and 3) provides proteins that enable the virion to penetrate the host cell membrane and, in some cases, to inject the infectious nucleic acid into the cell's cytoplasm. Under the right conditions, viral RNA in a liquid suspension of protein molecules will self-assemble a capsid to become a functional and infectious virus.

Envelope - Many types of virus have a glycoprotein envelope surrounding the nucleocapsid. The envelope is composed of two lipid layers interspersed with protein molecules (lipoprotein bilayer) and may contain material from the membrane of a host cell as well as that of viral origin. The virus obtains the lipid molecules from the cell membrane during the viral budding process. However, the virus replaces the proteins in the cell membrane with its own proteins, creating a hybrid structure of cell-derived lipids and virus-derived proteins. Many viruses also develop spikes made of glycoprotein on their envelopes that help them to attach to specific cell surfaces.

Nucleic Acid - Just as in cells, the nucleic acid of each virus encodes the genetic information for the synthesis of all proteins. While the double-stranded DNA is responsible for this in prokaryotic and eukaryotic cells, only a few groups of viruses use DNA. Most viruses maintain all their genetic information with the single-stranded RNA. There are two types of RNA-based viruses. In most, the genomic RNA is termed a plus strand because it acts as messenger RNA for direct synthesis (translation) of viral protein. A few, however, have negative strands of RNA. In these cases, the virion has an enzyme, called RNA-dependent RNA polymerase (transcriptase), which must first catalyze the production of complementary messenger RNA from the virion genomic RNA before viral protein synthesis can occur.

The Influenza (Flu) Virus - Next to the common cold, influenza or "the flu" is perhaps the most familiar respiratory infection in the world. In the United States alone, approximately 25 to 50 million people contract influenza each year. The symptoms of the flu are similar to those of the common cold, but tend to be more severe. Fever, headache, fatigue, muscle weakness and pain, sore throat, dry cough, and a runny or stuffy nose are 10

common and may develop rapidly. Gastrointestinal symptoms associated with influenza are sometimes experienced by children, but for most adults, illnesses that manifest in diarrhea, nausea, and vomiting are not caused by the influenza virus though they are often inaccurately referred to as the "stomach flu." A number of complications, such as the onset of bronchitis and pneumonia, can also occur in association with influenza and are especially common among the elderly, young children, and anyone with a suppressed immune system. The Human Immunodeficiency Virus (HIV) - The virus responsible for HIV was first isolated in 1983 by Robert Gallo of the United States and French scientist Luc Montagnier. Since that time, a tremendous amount of research focusing upon the causative agent of AIDS has been carried out and much has been learned about the structure of the virus and its typical course of action. HIV is one of a group of atypical viruses called retroviruses that maintain their genetic information in the form of ribonucleic acid (RNA). Through the use of an enzyme known as reverse transcriptase, HIV and other retroviruses are capable of producing deoxyribonucleic acid (DNA) from RNA, whereas most cells carry out the opposite process, transcribing the genetic material of DNA into RNA. The activity of the enzyme enables the genetic information of HIV to become integrated permanently into the genome (chromosomes) of a host cell.

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