Introduction

Viruses, like bacteria, are found everywhere. They are, however, much smaller. Before the germ theory of disease was established, people thought that diseases were caused by poisons; and, since the Latin term for poison is "virus," that is the name adopted. Pasteur often referred to bacteria as viruses. Then, as research showed that microorganisms were the actual cause of infectious diseases, various pathogenic microbes were identified and removed from the category of poisons (or viruses). Since viruses do not propogate well in an artificial culture medium, observing them did not take place until the "golden age of microbiology," beginning in the late 1800s. By this time, the term "virus" had become permanently associated with these agents, and the original meaning essentially lost. By the late 1940s, procedures had been developed that allowed identification of thirty-five viruses associated with human disease. During the following fifteen to twenty years, 500 more were added to the list. The list continues to grow.

Viral particles are not cells and cannot carry out functions of their own. Their genetic material can be either DNA or RNA, occurring as either a single strand (ss) or a double strand (ds). Some simpler viruses contain only a single molecule of nucleic acid and a protein coat. Other viruses may possess an envelope over a protein coat, while still others may have internal proteins and/or small projections called peplomers. One of the simplest virus is the T4 phage that infects the E. coli bacteria in the stomach.

Most viruses, regardless of the types of hosts they attack, have similar functions. The outermost part has a "code" by which the virus is able to recognize which cells to enter and infect. This explains why so few viruses cause disease in different species and why viruses are organ specific. For example, hepatitis viruses targets liver cells, HIV looks for particular binding sites or markers on white blood cells, viruses responsible for the common cold target cells in the respiratory tract. Herpes I viruses attack the skin and mucous membranes of the mouth and lips, and Herpes II viruses infect similar cells of the genitalia.

It is estimated that 20% of all cancers are now viral in origin. Most liver cancers can be traced back to the HBV (hepatitis B virus). Some leukemias are initiated by viruses similar to HIV. Almost all cervical cancers are associated with the papillomavirus. Many now think that many incidents of heart disease, mental disorders, diabetes, and arthritis may be the result of chronic viral infections. Some physical and personality characteristics can be influenced by persistent viruses that the immune system cannot handle. There is also evidence that chronic viral infections can affect the immune system, leading to slow degeneration of infected tissues. Several such immune-related diseases are now called slow virus infections. Two such are Creutzfeldt-Jakob disease and herpesvirus infections.

There are two types of proteins that help a virus enter the cell of a host. One is hemagglutinin, and the other is neuraminidase. There are twelve basic types of hemagglutinins, and three of these (H1, H2, H3) commonly occur in viruses that attack human cells. Similarly, there are nine neuraminidases with N1 and N2 found in human viruses. The Spanish flu of 1918 had hemagglutinin type I and neuraminidase type I (HINI). The Asian flu had H2N2 and the Hong Kong flu had H3N2. This is how scientists are able to identify new variations.

When a virus approaches a cell, the hemagglutinins bind to carbohydrates protruding from the cell's surface. The cell then envelops the virus, holding it inside a little bubble of membrane. The fluid inside this bubble is more acidic than anything the virus has encountered before causing the hemagglutinins to change shape. This causes the bubble to burst, throwing the viral RNA into the cell. Once inside, eight species of RNA set to work ordering the host cell to create new copies of the virus. In just a few hours, one infected cell can generate hundreds and thousands of new viruses. Viral methods of reproduction can be complicated, and can vary enough to either cause very mild symptoms or simply kill the host.

The complete virus particle is called a "viron" and can be in one of five basic shape categories -- spherical, cylindrical, brick, bullet, or tailed. Two substructures of viruses are viroids and prions. These behave in a manner similar to viruses, but their structures lack the protein capsids. Viroids are small, circular-stranded RNA molecules that are the smallest known pathogens. These mainly cause disease to crops. Prions are the other extreme from viroids. They have a distinct extracellular form that may be entirely protein. They apparently do not contain any nucleic acid, or, if it does, does not stay long enough to encode any of its protein. They are thought to be the responsible agent for "mad cow" and such related human diseases.

Viruses are relatively unresponsive to antibiotics and other "wonder drugs" that are so effective in treating bacteria. Recovery is dependent instead on the patient's own immune system response. Malnutrition is the most common cause of acquired immunodeficiency or reduced immune resistance to infections. A breakdown of the first barrier, the skin, results from deficiencies in protein, zinc, Vitamins A, C, and the B complex. With the lack of protein, a reduction in biosynthesis of lymphocytes and immunoglobulins or antibodies occurs. Thus, the cycle of malnourishment and disease begins, and, with each bout, the cycle broadens.

All forms of life seem to have specific viruses that act as parasites to them. The viruses that attack bacteria are called bacteriophages (phages for short), and are much easier to work with in a labatory setting than animal or plant viruses. The various types of viruses that infect animals are (from the largest to the smallest) as follows: paramyxovirus, myxovirus, adenovirus, rhabdovirus, coronavirus, togavirus, papovavirus, picornavirus.

General steps of animal viral replication:

  1. Attachment to the cell surface: This is a specific reaction, and only cells that have the correct receptor site can be infected by a specific virus. This phenomenon accounts for the ability of a virus to infect only a certain animal species or only a given tissue within the animal.

  2. Penetration into the cytoplasm: After attachment has occurred, the plasma membrane penetrates into the cytoplasm and forms a vacuole around the virus. This process is called pinocytosis.

  3. Release of viral nucleic acid: The viral capsid is broken down by cellular enzymes, and the nucleic acid is released. This procedure may occur in either the nucleus or the cytoplasm, depending on the type of virus.

  4. Transcription of viral nucleic acid: This process occurs in the cytoplasm for some viruses and in the nucleus for others.

  5. Translation of viral-directed nRNA: Cellular ribosomes, tRNA, amino acids, energy, etc., are used in this step to bring about synthesis of the proteins needed for the synthesis of new viral particles.

  6. Replication of viral nucleic acid: One or more proteins are produced under the direction of the viral genome function as enzymes for directing the synthesis of new viral nucleic acid molecules. The original viral nucleic acid molecule must serve as a template.

  7. Assembly of virus particles: Viruses do not replicate by dividing as cells do, but are assembled from pools of the viral nucleic acid and protein structure units. Many copies of a virus may be forming simultaneously within a single cell. Assembly may occur in the nucleus or cytoplasm, or partly in one and partly in the other area, depending on the type of virus. As the capsid forms, it encloses the viral nucleic acid, but this process is not efficient, and often the capsid forms without enclosing the nucleic acid. This is called an empty virus particle. Often enough viral building blocks are produced to make 10,000 to 20,000 new virus particles per infected cell. Because of the inefficient assembly only about 200-300 particles will be formed properly. Even so, the whole process may only take an hour or two, and several hundred offspring are more than enough for an effective means of reproduction.

  8. Release of viruses: Some viruses are released when the cell disintegrates as a result of the damage produced by the replication process. These viruses would have no envelopes. Other viruses migrate to a cell membrane and bud out through the membrane, which pinches off and remains attached to the virus forming an envelope. With some viruses, viral-directed proteins are formed and become embedded in the cell membrane and are thus encorporated into the envelope.

Viruses can be divided into at least six general classes based on the type of nucleic acid they contain and on the pathways they use to express their genetic information.

  1. Viruses with ds-DNA: The flow of information is ds-DNA to mRNA to protein. This classic pathway is seen in all higher forms of life.

  2. Viruses with ss-DNA: The flow of information is ss-DNA to ds-DNA to mRNA to protein. The ss-DNA must first be changed into ds-DNA done by cellular enzymes after the viral nucleic acid enters the cell. Thereafter, the flow of information is the same as in Class 1.

  3. Viruses with ds-RNA: The flow of information is ds-RNA to mRNA to protein. This class of viruses presents a unique problem because ds-RNA is not found in normal cells. Thus, no enzyme is present in a cell to direct the transcription of ds-RNA molecules. To solve this problem, these viruses direct the synthesis of a special enzyme that will transcribe mRNA from the ds-RNA molecule. This enzyme is packaged inside the viral capsid along with the ds-RNA.

  4. Viruses with ss-RNA of the same polarity as mRNA (simply called ss-RNA+): The information flow is mRNA to protein. The viral nucleic acid acts directly as mRNA once inside the cell and completely bypasses the regular step of transcription.

  5. Viruses with ss-RNA of the opposite polarity from mRNA (simply called ss-RNA-): The information flow is ss-RNA- to mRNA to protein. The information flow is ss-RNA- to mRNA to protein. As in class 3, this is a unique situation in which a function not found in a normal cell must be carried out -- that is, the transcription of mRNA from a ss-RNA molecule. It is, therefore, necessary to provide a specific enzyme to accomplish this task. These viruses carry this special enzyme and also direct its formation as part of their replication process.

  6. Viruses with ss-RNA+ and a special enzyme called Reverse Transcriptase or RNA-dependent-DNA polymerase: Some viruses in this class are associated with the induction of cancer in animals, and others cause the immunodeficiency syndrome (AIDS). These viruses change the genetic information on their ss-RNA molecule into a ds-DNA molecule, or in other words, move backward from the normal flow of genetic information. The information flow is ss-RNA to ss-DNA to ds-DNA to mRNA to protein. The enzyme reverse transcriptase is needed for the step from ss-RNA to ss-DNA. Normal cellular enzymes are able to direct the other functions. When the ds-DNA is formed, it may insert into the DNA of the host cell. Under certain conditions that are not well understood, some of the information in this inserted DNA may be transcribed and direct changes in the cell that may cause cancer. Under other conditions the inserted DNA may be transcribed and direct the information of new virus particles.