What are viral infections? |

How Viruses Work

Viruses are entities that infect the cells of all organisms. Some scientists classify viruses as living organisms based on their ability to reproduce inside an appropriate host cell. Yet, viruses lack cellular structure and have no metabolic capability of their own. They are completely dependent on host cells to reproduce. In addition, some viruses can be crystallized and thus have properties of complex molecules rather than of living organisms.

Viruses can be visualized only with an electron microscope. They are small in size, ranging from approximately 10 to 300 nanometers in either length or diameter. Because viruses cannot easily be seen within the host cells that they infect, studies of viral structure often utilize the extracellular form of the virus, called the viral particle or virion.

Viruses are quite variable with respect to size, shape, and biological properties, but they do have some common features. All viruses contain a genome, which is genetic material in the form of either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). A protein coat known as a
capsid that is composed of protein subunits called capsomeres protects the genome of a virus. The capsid is arranged either into a symmetrical structure with spherical (round) or up to twenty-sided (icosahedral) symmetry. Alternatively, the capsid can assume a helical shape.

Some viruses contain additional protein structures that aid in their attachment and penetration of host cells. Other viruses, especially the ones that infect animal cells, are surrounded by a complex membrane structure known as the envelope. While the lipids in the envelope are derived from host cells, the proteins and glycoproteins contained in the envelope are usually viral-specific structures that are encoded by the genetic material of the virus. In animal viruses, the genetic material and protein coat, together called the nucleocapsid, constitute the core of the virus. In addition to these features, some viruses carry enzymes that are necessary for the virus to infect a host cell or to replicate.

Most viruses can infect only one type of host; that is, they display species specificity. The virus that causes rabies is a notable exception since it can infect a variety of mammalian species. All types of organisms—bacteria, protozoa, fungi, plants, and animals—are known to be hosts to viruses. Viruses that infect bacteria are called bacteriophages, or phages. The elucidation of many of the aspects of viral structure and the stages of viral infection was derived from the study of the mechanism by which phages infect their specific bacterial hosts.

Slow virus diseases are a class of viruses that reproduce very slowly, often over months or years. They are difficult to study. A common result of slow virus infections is a condition called spongiform encephalopathy, which is a degeneration of brain cells that ultimately causes death. Recent research has shown that slow viruses cause such diseases as kuru and Creutzfeldt-Jakob disease (CJD)
in humans and scrapie in sheep.

Several steps have been identified in the process by which viruses infect host cells. Because they lack motility, viruses must come into contact with host cells by chance. They are transmitted from host to host in the same ways as other microorganisms: through air, water, or food or by physical contact. A common mode of transmission is by aerosols produced when an infected individual coughs, sneezes, or breathes. Virions in the aerosols gain access to the host by means of the respiratory system. Common cold and influenza viruses are transmitted in this manner, as are the viruses that cause common childhood diseases such as chickenpox, measles, and mumps. As a result, these viruses are very contagious; they are easily spread from person to person.

Some viruses, such as the
poliomyelitis (polio) virus, can be transmitted in contaminated food or water. The virus gains entry to the host through the mouth and digestive system. Other viruses will also gain entry after contact, which may be direct (person to person) or indirect (via an inanimate object). Viruses will also enter a host if they are directly introduced into the bloodstream, which can occur via a cut or wound or through use of a contaminated needle.
Hepatitis B virus and the
Human immunodeficiency virus (HIV), which causes Acquired immunodeficiency syndrome (AIDS), can infect individuals in this manner. Transmission of these viruses occurs at a high rate among intravenous drug users who share needles. In addition to the above methods of transmission, mosquitoes may transmit viruses such as the encephalitis virus and the yellow fever virus.

All viruses must first attach themselves to their respective host cells. This phase of viral infection is sometimes referred to as adsorption. The attachment process is very specific and is controlled (mediated) by receptors present on the host cell, most of which are glycoproteins. It is the specific nature of this attachment process that accounts for the fact that a virus will infect host cells of only one species. Some viruses are also specific for the type of host cell to which they will adsorb. For example, poliovirus adsorbs only to cells of the central nervous system and gastrointestinal tract.

Following adsorption, the virus penetrates the host cell. In the case of bacteriophages, only the viral genome reaches the interior of the host cell; the protein coat of the virus remains outside. In contrast, the entire animal virus penetrates its host cell. Once inside, the viral genome is separated from the protein coat and envelope. During this stage of viral infection, the virus cannot be visualized by electron microscopy.

The viral genome is responsible for the next stages of viral infection. Many viruses begin a process that will eventually result in the replication of the viral genome and the production of progeny viruses. These viruses are referred to as lytic viruses because the death and lysis of the host cell accompany infection. The infecting lytic virus uses many of the host cell’s biochemical processes to replicate its DNA or RNA. It also causes the host to make proteins that will constitute the capsids of the newly made viruses. New viral particles assemble spontaneously. In many cases, hundreds of these progeny will be released as the host cell disintegrates. These newly produced viruses are then available to infect other cells. This type of virus causes diseases such as chickenpox and polio. In some cases, progeny viruses are continuously shed from host cells. The host cell remains viable for long periods of time and releases large numbers of viruses.

Some viruses do not produce progeny after they penetrate host cells. Instead of being used to produce new viruses, the genetic material of these viruses becomes part of the host cell genome in a process called integration. These viruses are referred to as lysogenic or temperate viruses. In order for these viruses to integrate into the host cell genome, they must either consist of double-stranded DNA or be capable of forming double-stranded DNA within the host cell. RNA viruses that are capable of lysogeny contain an enzyme known as reverse transcriptase that enables the virus to produce a DNA copy of the viral RNA. These viruses are known as
retroviruses. Several medically important viruses, such as some tumor viruses and HIV, belong to this category.

Although integrated into the viral genome, lysogenic viruses do not multiply to produce new viral particles. They remain in an apparently latent state. There is evidence, however, that these viruses can make some types of protein and, in some cases, can alter the properties of their host cells. For example, when a virus called SV40 integrates into the genome of certain host cells, it will cause these cells to divide rapidly and grow in a manner that resembles tumor cells. Not all lysogenic viruses remain latent. Ultraviolet light is known to cause latent herpesvirus to switch to a lytic mode of infection, an effect known as induction. Other factors, such as stress, may also be responsible for viral induction.

Diagnosis and Treatment

The extent of a viral disease can usually be explained by the biological properties of the particular virus involved. Some viral infections may be mild, such as the common cold, or entirely unnoticed. Other viral infections can be more serious, debilitating, or even fatal, such as polio, influenza, and AIDS. In some cases, viral infection is acute; an individual is sick for a short period of time and then fully recovers. Other viral infections are chronic; the virus persists for long periods of time. The disease that it causes periodically erupts and then subsides.

Diagnosis of viral diseases often relies on an analysis of the symptoms associated with each type of viral infection. Some viral illnesses cause typical rashes such as those seen in chickenpox, measles, and rubella. Influenza virus infection results in typical flulike symptoms, including throat pain, fever, and muscle aches. It is much more difficult to diagnose viral infections when the virus is latent or not actively causing damage to the host. Sometimes it is important to detect individuals who are infected with a latent virus or who are not symptomatic. Such individuals may be carriers of the virus and thus have the potential to transmit the disease to others. It is possible to identify such individuals by testing for the presence of viral proteins or by examining their immune response to the virus.

The major host defense against viral infections in higher organisms is the immune system
. Cells of the immune system recognize many disease-causing viruses, either as virions circulating within the host or by the presence of virus-specific proteins on infected host cells. In either case, the virus is eliminated, although damage to host cells is sometimes a natural consequence of this type of protection. This active immune response against the virus will often result in lifelong protection from subsequent infections by the same virus. It is extremely rare for a person who has recovered from measles or mumps to have another occurrence of that particular disease.

Some viruses are not completely eliminated when recovery occurs. Varicella zoster virus is the cause of chickenpox, a common childhood disease. Chickenpox usually runs its course in about two weeks, and complete clinical recovery is observed. Yet, the virus is not necessarily eliminated. It has been tracked to the nervous system, where it can remain dormant for decades. The virus can be reactivated, usually in older adults or in those individuals whose immune systems are compromised. It will travel via the nerves and cause
shingles (herpes zoster). Shingles is a condition characterized by a burning rash, itching, tingling, and pain that may be quite severe.

Vaccines. Vaccines protect against viral infections by utilizing the host’s own immune system. For use in vaccines, the virus is either inactivated, and thus is no longer capable of causing an infection, or infectious but of a much milder strain. Viruses are commonly inactivated for vaccine preparation by chemical treatments that essentially kill the virus. The virus is then no longer able to infect and multiply within host cells. These types of vaccines must be administered at repeated time intervals (months or years, depending on the vaccine) to ensure a sufficient level of immunity.

Live viruses are used in some vaccines, but the harmful or pathogenic form of the virus is never employed. Instead, a weaker version of the virus is selected. These weaker variants, called attenuated strains, can sometimes be found when the virus is grown under laboratory conditions. The advantage of live viral vaccines is that the virus can multiply within the host and cause a significantly higher stimulation of the host’s immune system than is usually seen with inactivated viral vaccines. Attenuated strains of the poliovirus are used to produce the oral polio vaccine that is commonly administered to infants. In rare cases, serious problems do occur with live vaccines. A few individuals among the millions who have been vaccinated, or their family contacts, have been known to develop polio as a result of exposure to the live polio vaccine.

Another method of vaccine preparation involves the use of parts of the viral envelope, particularly the viral-coded proteins. These proteins can be mass-produced using modern genetic engineering
technology and then incorporated into various vaccine preparations. This method has the advantage of reducing the risks involved with live vaccines.

The important result of vaccination is that the immune system is stimulated to recognize the virus and thus eliminate its harmful form when the virus is next encountered. Vaccination programs have been highly effective in decreasing the incidence of viral diseases in countries where they are administered. The most striking success of a major vaccination program was the virtual global elimination of naturally occurring smallpox, declared official by the World Health Organization in 1980.

For some viral infections, the immune system does not offer adequate protection from the harmful effects of the virus. In still other cases, effective vaccines that offer long-term protection against viral infection have not been developed. With some viral infections, an encounter with the virus does not guarantee immunity from future infections: the virus is able to alter its envelope proteins and thus appears different to the immune system when it is encountered again. This is the case with influenza viruses.

Chemical agents. Chemical antiviral agents have also been developed. These chemical agents have been useful because they limit or inhibit important steps in the viral reproductive cycle. For example, acyclovir inhibits the replication of viral DNA in herpesviruses. Among the problems encountered with the use of these chemical agents, however, are their restricted action (they work only for certain viruses) and their toxic effects on the host.

A naturally produced agent with antiviral activity is interferon. Interferon is actually a group of proteins produced by the host during a viral infection. These proteins are active only in the host species in which they are produced. They have the ability to interfere with viral multiplication and are therefore potentially useful agents in the treatment of viral infection and certain human cancers.

Cancer and viruses. The link between viruses and cancer, induced in experimental animals, was established in the early part of the twentieth century. The role of viruses as causative agents of human cancers has been less conclusive. Many viruses are associated with human cancers. They are often integrated into the genomes of cancer cells. Yet, the presence of a virus and its association with a certain type of cancer do not constitute proof that the virus is actually responsible for the cancerous condition. There is evidence that a type of liver cancer, hepatocellular carcinoma, may be caused by hepatitis B or C virus. A specific form of leukemia has been linked to human T-cell leukemia viruses. The
Epstein-Barr virus is associated with a rare type of cancer, Burkitt’s lymphoma. Viruses may be involved in many other types of human cancer, along with other genetic and environmental factors.

The growing evidence for the involvement of viruses in human cancers, either directly or indirectly, provides further impetus for developing an understanding of the biology of these viruses, as well as methods to protect individuals from infection. Molecular biologists continue to elucidate the strategies by which cancer viruses gain entry into host cells and alter the properties and functions of these cells. Understanding such events will provide important clues that could be utilized to interrupt the processes that cause normal cells to become cancer cells.

Prevention. Very few antiviral agents have proven effective in combating viral illnesses. One of the best approaches in dealing with viral infection is prevention. This can be accomplished by identifying the mode of transmission of the virus and developing measures to block the transmission whenever possible. The most powerful method of preventing viral diseases, however, is through the use of vaccines to immunize individuals against viral infection. Vaccine programs have been tremendously successful in eliminating smallpox worldwide and in greatly reducing the number of new cases of polio and chickenpox throughout the Western Hemisphere and Europe. Continued efforts are needed to produce safe and effective vaccines. These vaccines must also be stable and easily administered so that they can be used in parts of the world where populations need protection from serious viral diseases.

Preventive measures cannot be used in all cases. For example, it is extremely difficult to block the transmission of viruses that are carried in the air. There are also many viral diseases for which safe vaccines may not be available. Furthermore, some viruses are able to evade the immune defenses of the host, thus greatly reducing the usefulness of a vaccine. The influenza virus has a strategy for escaping detection by the host’s immune system. This virus is able to alter its envelope proteins so that the newer forms are no longer recognized by the immune system of an individual who has recovered from a previous bout with the flu. Thus, an individual who has had one strain of flu is susceptible to another occurrence of the illness caused by a different strain. Although flu vaccines have been developed, their usefulness is limited by the changing nature of the virus.

Perspective and Prospects

From their discovery as the causative agent of tobacco mosaic disease in the late 1890s by the Dutch microbiologist Martinus Beijernick, viruses have been implicated in numerous plant and animal diseases. Human diseases caused by viruses range from very mild to fatal and are often difficult to treat. Epidemics caused by viruses have plagued humankind for centuries. Outbreaks of smallpox, polio, yellow fever, and other viral diseases were once quite commonplace. Viral illnesses such as influenza still appear yearly in epidemic proportions. A severe worldwide outbreak of influenza was responsible for the deaths of twenty million people between 1918 and 1919.

The virus that causes AIDS, the human immunodeficiency virus (HIV), has the potential to cause millions of deaths worldwide. It is spread relatively easily, and the time between exposure and apparent disease can be a decade or longer. Many experts are working to create a vaccine for HIV/AIDS.

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