| Contents | Previous | Next |
The discovery of new viral classifications is changing our view of the microbial world. Dr. Charles Sieber has said “We haven’t even begun to scratch the surface. The numbers are mind-boggling. If you put every virus particle on earth together in a row, they would form a line10 million light-years long. People, even most biologists, don’t have a clue. The general public thinks genetic diversity is us and birds and plants and animals, and that viruses are just HIV and the flu. But most of the genetic material on this planet is a virus. They and their ability to interact with organisms and move genetic material around are the major players in driving speciation, in determining how organisms even become what they are.” (Siebert, March 2006.)
The word virus comes from the Latin word for “poison.” Adolf Meyer first detected what was ultimately identified as a virus in the 1880s when he was studying a tobacco disease that caused leaves to have a mottled appearance. Stanley confirmed his hypothesis when he crystallized the substance in 1933. The first atomic resolution structure of a virus was not solved until 1978 when that of tomato bushy stunt virus appeared.
Researchers have characterized some 4,000 viruses from several dozen distinct families. That is a tiny fraction of the number of viruses on earth. Scientists estimate that they have discovered and documented less than one percent of all the living things.
In the last two years, J. Craig Venter, the geneticist who decoded the human genome, has circled the globe in his sailboat and sampled ocean water every couple of hundred miles. Each time he dipped a container overboard; he discovered new viruses—so many that he increased the number of known genes 10-fold. (Venter, 2004.)
It is clear that viruses do not have all of the characteristics of what we humans call a living organism. Viruses are entities that consist only of small bits of proteins and nucleic acids, (virion or viral particle) and appear to be in a “gray” area between the living and the non-living world. A virus outside of its host may also be called a virion. The complete virion is little more than a gene transporter.
Viruses are small microbes; they can be as much as 10,000 times smaller than bacteria. Outside of the appropriate host they are inert. Since viruses are not cells they can’t metabolize nutrients, produce and excrete wastes, move around on their own, or reproduce unless they are inside another organism’s cells. Viruses usually are too small (100–2,000 Angstrom units) to be seen with the light microscope and thus must be studied by electron microscopes.
We know that virus components are a nucleic acid genome, either DNA or RNA, either single or double stranded, and positive or negative. The “structure” is surrounded by a capsid (protein coat). The shape of the capsid is either spherical or helical. These structures can range in size from less than 20 nanometers up to 400 nanometers and are composed of viral proteins.
The virus is surrounded by a protein coat, or outer coat that is called the viral envelope. The viral envelope consists of an inner layer of lipids and proteins as well as viral glycoproteins. Glycoproteins are macromolecules composed of proteins and carbohydrates. The components of the envelope (i.e. glycoprotein) and capsid provide the mechanism for injecting the viral genome into a host cell, that is, they use these components to attach to and infect cells.
For example, the HIV (human immune deficiency virus) has a diameter of 1/10,000 of a millimeter. Its viral outer coat is the envelope, which is composed of two layers of fatty molecules (lipids). Within the viral envelope there are proteins (glycoproteins). Not all viruses have an envelope, as there are complex biochemical differences between viruses.
The unique characteristic that differentiates viruses from other organisms is the fact that they require other organisms to host themselves in order to survive. Hence they are deemed obligate parasites. They replicate by altering the genetic make up of a cell to start coding for materials required to make more viruses. By altering the cell instructions, more viruses can be produced, which in turn, can affect more cells and continue their existence as a species.
As we’ve seen, host cells can be from humans, animals, plants or bacteria, but each type of virus requires a specific type of host cell for its support system. Host cells can now be created in laboratories that deal with specific viruses. Viruses can also be cultivated by allowing them to grow on membranes from fertilized eggs.
Viruses are difficult targets for chemotherapy because they replicate only within host cells utilizing many of the host cell’s biosynthetic process. The similarity of host-directed and virus-directed processes makes it difficult to find antiviral agents specific enough to exert a greater effect on viral replication in infected cells than on functions in uninfected host cells.
Rift Valley Fever Virus (1930)
Eastern Equine Encephalitis Virus (1933)
Western Equine Encephalitis Virus (1936)
Venezuelan Equine Encephalitis Virus (1938)
California Encephalitis Virus (1943)
Hantaan Virus (1950)
Sindvis Virus (1952)
Chickungunya Virus (1956)
Kyasanur Forest Virus (1957)
Junin Virus (1958)
O’nyong-nyong Virus (1959)
La Cross Encephalitis Virus (1960)
Ross River Fever Virus (1960)
Oropouche Virus (1961)
Machupo Virus (1966)
Marburg Virus (1967)
Igbo Ora Fever Virus (1967)
Lassa Virus (1970)
Trivittatus Enecephalitis Virus (1970’s)
Rotavirus (1973)
Parvovirus B19 (1974)
Ebola Sudan Virus (1976)
Ebola Zaire Virus (1976)
Seoul Virus (1977)
Human T-Lymphotropic Virus (HTVL-1) 1980
Human T-Lymphotropic Virus (HTVL-2) 1982
Jamestown Canyon Encephalitis Virus (1983)
Human Immunodeficiency Virus (HIV 1) (1983)
Human Immunodeficiency Virus (HIV 2) (1985)
Human Herpesvirus-6 (HHH-6) (1986)
Hepatitis E Virus (1988)
Hepatitis C Virus (1989)
Hepatitis G Virus (1992)
Ebola Reston Virus (1989)
Guanarito Virus (1991)
Sin Nombre Hantavirus (1993)
Sabia Virus (1994)
Human Herpes Virus-8 (1995)
Ebola Ivory Coast Virus (1995)
For a virus to multiply it must obviously infect a cell. Viruses usually have a restricted host range — or animal type and cell type in which replication is possible.
Viruses need to make proteins with 3 sets of functions:
Viruses can be spread in the following exemplar ways:
Attachment — The virus attaches to receptors on the host cell wall.
Penetration — The nucleic acid of the virus moves through the plasma membrane and injects into the cytoplasm of the host cell. The capsid of a phage, (a bacterial virus), remains on the outside.
Replication — The viral genome contains all the information. Once inside the host cell, the virus induces the host cell to synthesize the necessary components for its replication. The newly synthesized viral components are assembled into new viruses.
Maturation — the maturation phase is when viral material accumulates exponentially in the cell or surrounding medium and Lysis happens: (Assembled viruses are released from the cell and can now infect other cells, and the process begins again). Virus production stops, but the genome remains present in the cell, examples include Epstein Barr Virus and herpes simplex virus.
Exit — cellular exit cell
For pathogenic viruses, there are a number of critical stages in replication which determine the nature of the disease they produce:
Entry into the host is the first stage in any virus infection, irrespective of whether the virus is pathogenic or not. In the case of pathogenic infections, the site of entry can influence the disease symptoms produced.
In high school biology we learned about the various groupings of organisms and those principals are applied to viruses as well. In summary they would be Domain, Kingdom, Phylum (animals) or Division (plants), class, order, family, genus, species. Since this is not a course in virology we will only mention the most general groupings, namely family, the virus genus, and some subviral agents such as viroids and prions and diseases they cause.
Virology is the study of viruses, complexes of nucleic acids and proteins that have the capacity for replication in animal, plant and bacterial cells. Virology is a complicated subject with extensive study required to examine the microscopic aspects of viruses. This writing is intentionally focused to provide a superficial introduction to some of the complexities and variations of viruses in order to foster an appreciation of the health issues that we face as a global entity and to identify the role of the nurse in the education of the public.
Viruses can be classified in several ways: by their geometry, by whether they have envelopes, by the identity of the host organism they can infect, by mode of transmission, or by the type of disease they cause. The most useful classification is probably by the type of nucleic acid the virus contains and its mode of expression.
Viruses are classified on the basis of morphology, chemical composition and mode of replication. There is a universal system for classifying viruses established by the International Committee on Taxonomy of Viruses.
The taxonomy is broken down by order (virales being the highest recognized), then the family (viridae), then the subfamily (virinae) then the genus (virus) and finally the species.
An example might be the Ebola virus (discussed later) classified as:
All viruses consist of nucleic acid genome (either DNA or RNA, or both). There are RNA viruses and DNA viruses and they are grouped together according to their shapes and genetic materials.
Group 1: double-stranded DNA i.e., bacteriophage
Group 2 single-stranded DNA i.e., parvovirus
Group 3: double-stranded RNA i.e., rotaviruses
Group 4: positive single-stranded RNA i.e., conavirus (SARS)
Group 5: negative single-stranded RNA i.e., mumps
Group 6: reverse transcription viruses i.e., retrovirus HIV 1
These are yet another form of viruses that are smaller than viruses and have some of their properties. They are only briefly mentioned as this is part of a viral overview.
Parvoviruses are smaller than most viruses, consisting of a protein coat and a single strand of DNA. Parvoviruses are among the smallest, simplest eukaryotic viruses and were discovered in the 1960’s.
Essentially, they fall into two groups: defective viruses that are dependent on helper virus for replication, and autonomous/replication-competent viruses. In all, more than 50 parvoviruses have been identified. Parvoviruses cause infections in a wide variety of birds and mammals, but 70-90% of most human populations are seropositive.
The known human parvovirus is referred to as B19. In 1981 its association with aplastic crisis in children was first realized. Feline parvovirus and Canine parvovirus have emerged during the last decade as serious veterinary pathogens. Vaccines against both now exist and are widely used.
The mimivirus represents a new family of “nucleocytoplasmic” viruses (large merged DNA’s). A mimivirus is a giant virus with mature particles of 400 nm in diameter. It has 800,000 bases and 900 genes, first discovered in 1992 and identified by researchers in Marseille, France in 2003. (The typical virus is 200 nanometers, or 8 millionths of an inch wide). Recently scientists have declared that as the virus particle is capable of generating its own proteins, it is “alive”, and is very similar to bacteria. (Science Magazine March 28, 2003).
Viruses that invade bacteria are called virusoids or satellite RNAs. They depend on a helper virus for replication. These include Various, Prions, Virusoids.
Viroids are infectious molecules; viroids contain only RNA, lack an envelope and capsid. Recently a viroid has been linked to hepatitis D.
Bacteriophages are viruses that attack bacteria. Bacteriophages have proteins in their capsid that bind to receptor molecules in their host’s cell wall. The lysogenic effect allows for viral entry and reproduction within cells. This is an entire study within itself, and only introduced here.
Thus the lysogenic effect is what phages do, that is, they can either be lytic (causing an immediate rupture of the bacterial cell) or can be lysogenic (the bacteriophage integrates with the bacterial DNA). When it is lysogenic, it remains dormant until the environmental stresses trigger the assembly and release of genetic material (the virion, or genetic material, is injected into the host’s cell) to rupture the cells.
The lysogenic phage, or dormant stage is also known as a prophage. The virus may use the host cell to reproduce at the time of infection and then kill the host. Bacteriophages are often specific to a specific strain of bacteria and may not be able to infect all members of a given species.
“Phages” (the common shorthand term for bacteriophages) infect only specific bacteria. Some phages are virulent and within a short time lyse (destroy) the cell, releasing new phages. Some phages (so-called temperate phages) can instead enter a relatively harmless state, either integrating their genetic material into the chromosomal DNA of the host bacterium or establishing themselves as plasmids.
Phages play an important role in molecular biology as cloning vectors to insert DNA into bacteria.
Bacteriophages capable of a lysogenic life cycle are termed temperate phages. When a temperate phage infects a bacterium, it can either replicate by means of the lytic life cycle and cause lysis of the host bacterium, or, it can incorporate its DNA into the bacterium’s DNA and become a noninfectious prophage.
In the latter case, the cycle begins by the phage adsorbing to the host bacterium or lysogen and injecting its genome as in the lytic life cycle. However, the phage does not shut down the host cell. Instead, the phage DNA inserts or integrates into the host bacterium’s DNA.
The following is a guide of how a bacteriophage takes control of its host cell and reproduces itself.
Independently, both Frederick Twort (1915) and Félix d’Herelle (1917) discovered phages. D’Heurelle continued his research and development in Stalin’s time and Russian scientists continued to develop already successful phage therapy to treat the wounds of soldiers in field hospitals. Phage therapy progressed and has been used since the 1940s in the former Soviet Union as an alternative to treating bacterial infections — because killing bacteria is what phages do best.
Phages for more than 100 bacterial genera have been isolated today (Ackermann, 1995.) There is an extensive library of research into specific phages and their therapeutic uses in the Tbilisi Institute in Georgia, in the former Soviet Union. The development of bacterial strains that are resistant to multiple drugs has led western medical researchers to re-evaluate phages as alternatives to the use of antibiotics. A phage uses the bacterium’s machinery and energy to produce more phage until the bacterium is destroyed and phage is released to invade surrounding bacteria.
The treatment is effective by using the phage virus to infect and kill specific bacteria while not interacting with the surrounding human tissue or other harmless bacteria. The virus replicates quickly so a single, small dose is usually sufficient.
Research groups in the west are seeking to develop broad-spectrum phage and targeted MRSA treatments in a variety of forms including impregnated dressings for wounds. “I strongly believe phage could become an effective antibacterial tool,” said, Carl Merril, Chief of the Laboratory of Biochemical Genetics, National Institute of Mental Health, NIH. (2002)
The clearest benefit of phage therapy is that bacteria cannot easily develop resistance to phages, so the technique is likely to be devoid of the problems similar to antibiotic resistance.
Secondly bacteriophages are very specific, targeting only particular strains of bacteria. Traditional antibiotics have a wide-ranging effect, meaning that they kill both harmful and useful bacteria. The specificity of the phage reduces the chance that useful bacteria are killed when fighting an infection.
Bacteriophages, phages for short, are viruses that prey upon bacteria. They have a simple structure, and once a phage latches onto a bacterium it injects its genetic material into the bacterium. The bacterium makes copies of itself and then lyses (explodes). Physicians have used phages as medical treatment for illnesses ranging from cholera to typhoid fever in the 1900’s. When antibiotics became mainstream phage therapy faded in the west. However, Europeans and the Soviet Union continued the potential healing properties of phages. Recently due to MRSA, VRE and VRSA (antibiotic resistant bacteria) the idea of phage therapy is being reconsidered.
Many believe today that phage therapy was not proven to work; however, others believe that it was not given enough of a trial, and a reassessment is warranted. Among the benefits are: few side effects have been reported in phage therapeutic history, appropriately selected phages can be used prophylactically to help prevent bacterial disease, and phage can be used either independently or in conjunction with other antibiotics. Phages for more than 100 bacterial genera have been isolated. (Ackermann, H. W.1995,) After considerably more research is conducted in the West, it appears that now is a good time to look more carefully at the potential of phage therapy as the increasing problems of resistant pathogens increase.