VIRUSES AND RESPONSES TO VIRAL INFECTION
There are a number of different viruses that challenge the human immune system and that may produce disease in humans. In common, viruses are small, infectious agents that consist of a core of genetic material—either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA)—surrounded by a shell of protein. Although precise mechanisms vary, viruses cause disease by infecting a host cell and commandeering the host cell's synthetic capabilities to produce more viruses. The newly made viruses then leave the host cell, sometimes killing it in the process, and proceed to infect other cells within the host. Because viruses invade cells, drug therapies have not yet been designed to kill viruses, although some have been developed to inhibit their growth. The human immune system is the main defense against a viral disease.
Bacterial viruses, called bacteriophages, infect a variety of bacteria, such as Escherichia coli, a bacteria commonly found in the human digestive tract. Animal viruses cause a variety of fatal diseases. Acquired Immunodeficiency Syndrome (AIDS) is caused by the Human Immunodeficiency Virus (HIV); hepatitis and rabies are viral diseases; and hemorrhagic fevers, which are characterized by severe internal bleeding, are caused by filoviruses. Other animal viruses cause some of the most common human diseases. Often these diseases strike in childhood. Measles, mumps, and chickenpox are viral diseases. The common cold and influenza are also caused by viruses. Finally, some viruses can cause cancer and tumors. One such virus, Human T-cell Leukemia Virus (HTLV), was only recently discovered and its role in the development of a particular kind of leukemia is still being elucidated.
Although viral structure varies considerably between the different types of viruses, all viruses share some common characteristics. All viruses contain either RNA or DNA surrounded by a protective protein shell called a capsid. Some viruses have a double strand of DNA, others a single strand of DNA. Other viruses have a double strand of RNA or a single strand of RNA. The size of the genetic material of viruses is often quite small. Compared to the 100,000 genes that exist within human DNA, viral genes number from 10 to about 200 genes.
Viruses contain such small amounts of genetic material because the only activity that they perform independently of a host cell is the synthesis of the protein capsid. In order to reproduce, a virus must infect a host cell and take over the host cell's synthetic machinery. This aspect of viruses—that the virus does not appear to be "alive" until it infects a host cell—has led to controversy in describing the nature of viruses. Are they living or non-living? When viruses are not inside a host cell, they do not appear to carry out many of the functions ascribed to living things, such as reproduction, metabolism, and movement. When they infect a host cell, they acquire these capabilities. Thus, viruses are both living and non-living. It was once acceptable to describe viruses as agents that exist on the boundary between living and non-living; however, a more accurate description of viruses is that they are either active or inactive, a description that leaves the question of life behind altogether.
All viruses consist of genetic material surrounded by a capsid; but variations exist within this basic structure. Studding the envelope of these viruses are protein "spikes." These spikes are clearly visible on some viruses, such as the
influenza viruses; on other enveloped viruses, the spikes are extremely difficult to see. The spikes help the virus invade host cells. The influenza virus, for instance, has two types of spikes. One type, composed of hemagglutinin protein (HA), fuses with the host cell membrane, allowing the virus particle to enter the cell. The other type of spike, composed of the protein neuraminidase (NA), helps the newly formed virus particles to bud out from the host cell membrane.
The capsid of viruses is relatively simple in structure, owing to the few genes that the virus contains to encode the capsid. Most viral capsids consist of a few repeating protein subunits. The capsid serves two functions: it protects the viral genetic material and it helps the virus introduce itself into the host cell. Many viruses are extremely specific, targeting only certain cells within the plant or animal body. HIV, for instance, targets a specific immune cell, the T helper cell. The cold virus targets respiratory cells, leaving the other cells in the body alone. How does a virus "know" which cells to target? The viral capsid has special receptors that match receptors on their targeted host cells. When the virus encounters the correct receptors on a host cell, it "docks" with this host cell and begins the process of infection and replication.
Most viruses are rod-shaped or roughly sphere-shaped. Rod-shaped viruses include tobacco mosaic virus and the filoviruses. Although they look like rods under a microscope, these viral capsids are actually composed of protein molecules arranged in a helix. Other viruses are shaped somewhat like spheres, although many viruses are not actual spheres. The capsid of the adenovirus, which infects the respiratory tract of animals, consists of 20 triangular faces. This shape is called an icosahedron. HIV is a true sphere, as is the influenza virus.
Some viruses are neither rod-nor sphere-shaped. The poxviruses are rectangular, looking somewhat like bricks. Parapoxviruses are ovoid. Bacteriophages are the most unusually shaped of all viruses. A bacteriophage consists of a head region attached to a sheath. Protruding from the sheath are tail fibers that dock with the host bacterium. Bacteriophage structure is eminently suited to the way it infects cells. Instead of the entire virus entering the bacterium, the bacteriophage injects its genetic material into the cell, leaving an empty capsid on the surface of the bacterium.
Viruses are obligate intracellular parasites, meaning that in order to replicate, they need to be inside a host cell. Viruses lack the machinery and enzymes necessary to reproduce; the only synthetic activity they perform on their own is to synthesize their capsids.
The infection cycle of most viruses follows a basic pattern. Bacteriophages are unusual in that they can infect a bacterium in two ways (although other viruses may replicate in these two ways as well). In the lytic cycle of replication, the bacteriophage destroys the bacterium it infects. In the lysogenic cycle, however, the bacteriophage coexists with its bacterial host and remains inside the bacterium throughout its life, reproducing only when the bacterium itself reproduces.
An example of a bacteriophage that undergoes lytic replication inside a bacterial host is the T4 bacteriophage, which infects E. coli. T4 begins the infection cycle by docking with an E. coli bacterium. The tail fibers of the bacteriophage make contact with the cell wall of the bacterium, and the bacteriophage then injects its genetic material into the bacterium. Inside the bacterium, the viral genes are transcribed. One of the first products produced from the viral genes is an enzyme that destroys the bacterium's own genetic material. Now the virus can proceed in its replication unhampered by the bacterial genes. Parts of new bacteriophages are produced and assembled. The bacterium then bursts, and the new bacteriophages are freed to infect other bacteria. This entire process takes only 20–30 minutes.
In the lysogenic cycle, the bacteriophage reproduces its genetic material but does not destroy the host's genetic material. The bacteriophage called lambda, another E. coli-infecting virus, is an example of a bacteriophage that undergoes lysogenic replication within a bacterial host. After the viral DNA has been injected into the bacterial host, it assumes a circular shape. At this point the replication cycle can become either lytic or lysogenic. In a lysogenic cycle the circular DNA attaches to the host cell genome at a specific place. This combination host-viral genome is called a prophage. Most of the viral genes within the prophage are repressed by a special repressor protein, so they do not encode the production of new bacteriophages. However, each time the bacterium divides, the viral genes are replicated along with the host genes. The bacterial progeny are thus lysogenically infected with viral genes.
Interestingly, bacteria that contain prophages can be destroyed when the viral DNA is suddenly triggered to undergo lytic replication. Radiation and chemicals are often the triggers that initiate lytic replication. Another interesting aspect of prophages is the role they play in human diseases. The bacteria that cause diphtheria and botulism both harbor viruses. The viral genes encode powerful toxins that have devastating effects on the human body. Without the infecting viruses, these bacteria may well be innocuous. It is the presence of viruses that makes these bacterial diseases so lethal.
Scientists have classified viruses according to the type of genetic material they contain. Broad categories of viruses include double-stranded DNA viruses, single-stranded DNA viruses, double-stranded RNA viruses, and single stranded RNA viruses. For the description of virus types that follows, however, these categories are not used. Rather, viruses are described by the type of disease they cause.
Poxviruses are the most complex kind of viruses known. They have large amounts of genetic material and fibrils anchored to the outside of the viral capsid that assist in attachment to the host cell. Poxviruses contain a double strand of DNA.
Viruses cause a variety of human diseases, including smallpox and cowpox. Because of worldwide vaccination efforts, smallpox has virtually disappeared from the world, with the last known case appearing in Somalia in 1977. The only places on Earth where smallpox virus currently exists are two labs: the Centers for Disease Control in Atlanta and the Research Institute for Viral Preparation in Moscow. Prior to the eradication efforts begun by the World Health Organization in 1966, smallpox was one of the most devastating of human diseases. In 1707, for instance, an outbreak of smallpox killed 18,000 of Iceland's 50,000 residents. In Boston in 1721,
smallpox struck 5,889 of the city's 12,000 inhabitants, killing 15% of those infected.
Edward Jenner (1749–1823) is credited with developing the first successful vaccine against a viral disease, and that disease was smallpox. A vaccine works by eliciting an immune response. During this immune response, specific immune cells, called memory cells, are produced that remain in the body long after the foreign microbe present in a vaccine has been destroyed. When the body again encounters the same kind of microbe, the memory cells quickly destroy the microbe. Vaccines contain either a live, altered version of a virus or bacteria, or they contain only parts of a virus or bacteria, enough to elicit an immune response.
In 1797, Jenner developed his smallpox vaccine by taking infected material from a cowpox lesion on the hand of a milkmaid. Cowpox was a common disease of the era, transmitted through contact with an infected cow. Unlike smallpox, however, cowpox is a much milder disease. Using the cowpox pus, he inoculated an eight-year-old boy. Jenner continued his vaccination efforts through his lifetime. Until 1976, children were vaccinated with the smallpox vaccine, called vaccinia. Reactions to the introduction of the vaccine ranged from a mild fever to severe complications, including (although very rarely) death. In 1976, with the eradication of smallpox complete, vaccinia vaccinations for children were discontinued, although vaccinia continues to be used as a carrier for recombinant DNA techniques. In these techniques, foreign DNA is inserted in cells. Efforts to produce a vaccine for HIV, for instance, have used vaccinia as the vehicle that carries specific parts of HIV.
Herpesviruses are enveloped, double-stranded DNA viruses. Of the more than 50 herpes viruses that exist, only eight cause disease in humans. These include the human herpes virus types 1 and 2 that cause cold sores and genital herpes; human herpes virus 3, or varicella-zoster virus (VZV), that causes chickenpox and shingles; cytomegalovirus (CMV), a virus that in some individuals attacks the cells of the eye and leads to blindness; human herpes virus 4, or Epstein-Barr virus (EBV), which has been implicated in a cancer called Burkitt's lymphoma; and human herpes virus types 6 and 7, newly discovered viruses that infect white blood cells. In addition, herpes B virus is a virus that infects monkeys and can be transmitted to humans by handling infected monkeys.
Adenoviruses are viruses that attack respiratory, intestinal, and eye cells in animals. More than 40 kinds of human adenoviruses have been identified. Adenoviruses contain double-stranded DNA within a 20-faceted capsid. Adenoviruses that target respiratory cells cause bronchitis, pneumonia, and tonsillitis. Gastrointestinal illnesses caused by adenoviruses are usually characterized by diarrhea and are often accompanied by respiratory symptoms. Some forms of appendicitis are also caused by adenoviruses. Eye illnesses caused by adenoviruses include conjunctivitis, an infection of the eye tissues, as well as a disease called pharyngoconjunctival fever, a disease in which the virus is transmitted in poorly chlorinated swimming pools.
Human papoviruses include two groups: the papilloma viruses and the polyomaviruses. Human papilloma viruses (HPV) are the smallest double-stranded DNA viruses. They replicate within cells through both the lytic and the lysogenic replication cycles. Because of their lysogenic capabilities, HPV-containing cells can be produced through the replication of those cells that HPV initially infects. In this way, HPV infects epithelial cells, such as the cells of the skin. HPVs cause several kinds of benign (non-cancerous) warts, including plantar warts (those that form on the soles of the feet) and genital warts. However, HPVs have also been implicated in a form of cervical cancer that accounts for 7% of all female cancers.
HPV is believed to contain oncogenes, or genes that encode for growth factors that initiate the uncontrolled growth of cells. This uncontrolled proliferation of cells is called cancer. When the HPV oncogenes within an epithelial cell are activated, they cause the epithelial cell to proliferate. In the cervix (the opening of the uterus), the cell proliferation manifests first as a condition called cervical neoplasia. In this condition, the cervical cells proliferate and begin to crowd together. Eventually, cervical neoplasia can lead to full-blown cancer.
Polyomaviruses are somewhat mysterious viruses. Studies of blood have revealed that 80% of children aged five to none years have antibodies to these viruses, indicating that they have at some point been exposed to polyomaviruses. However, it is not clear what disease this virus causes. Some evidence exists that a mild respiratory illness is present when the first antibodies to the virus are evident. The only disease that is certainly caused by polyomavirses is called progressive multifocal leukoencephalopathy (PML), a disease in which the virus infects specific brain cells called the oligodendrocytes. PML is a debilitating disease that is usually fatal, and is marked by progressive neurological degeneration. It usually occurs in people with suppressed immune systems, such as cancer patients and people with AIDS.
The hepadnaviruses cause several diseases, including hepatitis B. Hepatitis B is a chronic, debilitating disease of the liver and immune system. The disease is much more serious than hepatitis A for several reasons: it is chronic and long-lasting; it can cause cirrhosis and cancer of the liver; and many people who contract the disease become carriers of the virus, able to transmit the virus through body fluids such as blood, semen, and vaginal secretions.
The hepatitis B virus (HBV) infects liver cells and has one of the smallest viral genomes. A double-stranded DNA virus, HBV is able to integrate its genome into the host cell's genome. When this integration occurs, the viral genome is replicated each time the cell divides. Individuals who have integrated HBV into their cells become carriers of the disease. Recently, a vaccine against HBV was developed. The vaccine is especially recommended for health care workers who through exposure to patient's body fluids are at high risk for infection.
Parvoviruses are icosahedral, single-stranded DNA viruses that infect a wide variety of mammals. Each type of parvovirus has its own host. For instance, one type of parvovirus causes disease in humans; another type causes disease in cats; while still another type causes disease in dogs. The disease caused by parvovirus in humans is called erythremia infectiosum, a disease of the red blood cells that is
relatively rare except for individuals who have the inherited disorder sickle cell anemia. Canine and feline parvovirus infections are fatal, but a vaccine against parvovirus is available for dogs and cats.
Orthomyxoviruses cause influenza ("flu"). This highly contagious viral infection can quickly assume epidemic proportions, given the right environmental conditions. An influenza outbreak is considered an epidemic when more than 10% of the population is infected. Antibodies that are made against one type of rhinovirus are often ineffective against other types of viruses. For this reason, most people are susceptible to colds from season to season.
These helical, enveloped, single-stranded RNA viruses cause pneumonia, croup, measles, and mumps in children. A vaccine against measles and mumps has greatly reduced the incidence of these diseases in the United States. In addition, a paramyxovirus called respiratory syncytial virus (RSV) causes bronchiolitis (an infection of the bronchioles) and pneumonia.
Flaviviruses (from the Latin word meaning "yellow") cause insect-carried diseases including yellow fever, an often-fatal disease characterized by high fever and internal bleeding. Flaviviruses are single-stranded RNA viruses.
The two filoviruses, Ebola virus and Marburg virus, are among the most lethal of all human viruses. Both cause severe fevers accompanied by internal bleeding, which eventually kills the victim. The fatality rate of Marburg is about 60%, while the fatality rate of Ebola virus approaches 90%. Both are transmitted through contact with body fluids. Marburg and Ebola also infect primates.
Rhabdoviruses are bullet-shaped, single-stranded RNA viruses. They are responsible for rabies, a fatal disease that affects dogs, rodents, and humans.
Retroviruses are unique viruses. They are double-stranded RNA viruses that contain an enzyme called reverse transcriptase. Within the host cell, the virus uses reverse transcriptase to make a DNA copy from its RNA genome. In all other organisms, RNA is synthesized from DNA. Cells infected with retroviruses are the only living things that reverse this process.
The first retroviruses discovered were viruses that infect chickens. The Rous sarcoma virus, discovered in the 1950s by Peyton Rous (1879–1970), was also the first virus that was linked to cancer. However, it was not until 1980 that the first human retrovirus was discovered. Called Human T-cell Leukemia Virus (HTLV), this virus causes a form of leukemia called adult T-cell leukemia. In 1983, another human retrovirus, Human Immunodeficiency Virus, the virus responsible for AIDS, was discovered independently by two researchers. Both HIV and HTLV are transmitted in body fluids.
