Variola Virus

Variola Virus

█ JULI BERWALD

Variola virus (or variola major ) is the virus that causes smallpox. The virus is one of the members of the poxvirus group (Poxviridae ) and it is one of the most complicated animal viruses. The variola virus is extremely virulent and is among the most dangerous of all the potential biological weapons.

The variola virus particle is shaped like a biconcave brick 200 to 400 nm long. Its inner compartment contains a highly compressed double strand of deoxyribonucleic acid as well as about 100 proteins and 10 viral enzymes. The enzymes are used in nucleic acid replication. Variola DNA contains about 250,000 base pairs, which make up about 200 genes. The depressions in the brick shape contain structures called lateral bodies, whose function is unknown. Two layers of membrane surround the outside of the virus. The outer layer is covered with spikes 20 nm long that are sometimes arranged helically.

The variola virus attaches to membrane receptors on the exterior of the host cell. The exact mechanisms involved in the binding to and penetration of the host membrane are not known. As it enters the cell, however, the virus loses its exterior membrane coat. Once inside the cell the interior membrane layer is removed and the virus's proteins, enzymes and DNA are released into the cytoplasm of the host cell where viral replication and assembly takes place. The first step in replicating the virus DNA involves a particular set of virus enzymes called Type I topiosomerase enzymes, which uncoil the compressed strands of variola DNA and aid in replicated the early genes. The second step of genome replication involves replicating the late genes. During the replication of the variola DNA, large concatamers are formed and subsequently cleaved to form individual virus genomes. The variola virus appears to be able to replicate itself without using any of the host cell's replication machinery. Individual viruses are assembled with the help of the Type I topiosomerase enzymes. It is thought that viral membranes are taken from the cisternae between the host's Golgi apparatus and endoplasmic reticulum. As new viruses are released from the host cell, this Golgi derived membrane is traded for the host's cell membrane. Release occurs about 12 hours after initial infection. The production of variola virus by the host cell usually results in host cell death.

Variola virus infects only humans and can be easily transmitted from person to person via the air. Inhalation of only a few virus particles is sufficient to establish an infection. Transmission of the virus is also possible if items such as contaminated linen are handled. The common symptoms of smallpox include chills, high fever, extreme tiredness, headache, backache, vomiting, sore throat with a cough, and sores on mucus membranes and on the skin. As the sores burst and release pus, the afflicted person can experience great pain. Males and females of all ages are equally susceptible to infection. Prior to smallpox eradication approximately one third of patients died—usually within a period of two to three weeks following appearance of symptoms.

The origin of the variola virus in not clear. However, the similarity of the virus and cowpox virus has prompted the suggestion that the variola virus is a mutated version of the cowpox virus. The mutation likely allowed to virus to infect humans. If such a mutation did occur, then it is possible that when early humans became more agricultural and less nomadic, there may have been selective pressure for the cowpox virus to adapt the capability to infect humans.

Vaccination to prevent infection by the variola virus was established in the 1700s. English socialite and public health advocate Lady Mary Wortley Montagu popularized the practice of injection with the pus obtained from smallpox sores as a protection against the disease. This technique became known as variolation. Late in the same century, Edward Jenner successfully prevented the occurrence of smallpox by an injection of pus from cowpox sores. This was the first vaccination. Vaccination against smallpox has been very successful, and the variola virus is the only pathogenic virus that has been eliminated from the natural environment. The last recorded case of smallpox infection was in 1977. Routine vaccination against smallpox was discontinued in the 1980s.

In the late 1990s, a resolution was passed at the World Health Assembly directing that the remaining stocks of variola virus be destroyed to prevent the reemergence of smallpox and the misuse of the variola virus as a biological weapon. At the time only two high-security laboratories were thought to contain variola virus stock: the Centers for Disease Control and Prevention in Atlanta, Georgia, and the Russian State Center for Research on Virology and Biotechnology in Koltsovo, Russia. However, this decision was postponed until 2002, and now the United States government has indicated its unwillingness to comply with the resolution because of security issues related to potential bioterrorism. Destruction of the stocks of variola virus would deprive countries of the material needed to prepare vaccine in the event of the deliberate use of the virus as a biological weapon. This scenario has gained more credence in the past decade, as terrorist groups have demonstrated the resolve to use biological weapons, including smallpox. In addition, intelligence agencies in several Western European countries issued opinions that additional stocks of the variola virus exist in other than the previously authorized locations.

█ FURTHER READING:

BOOKS:

Hopkins, D. R. The Greatest Killer: Smallpox in History. Chicago: University of Chicago Press, 2002.

Preston, R. The Demon in the Freezer. New York: Random House, 2002.

PERIODICALS:

Henderson, D. A., T. V. Inglesby, and J. G. Bartlett, et al. "Smallpox as a Biological Weapon: Medical and Public Health Management." Journal of the American Medical Association no. 281 (1999): 2127–37.

ELECTRONIC:

Centers for Disease Control and Prevention. "Smallpox." Public Health Emergency Preparedness and Response. November 26, 2002. <http://www.bt.cdc.gov/agent/smallpox/index.asp>(27 November 2002).

SEE ALSO

Biocontainment Laboratories
Biological and Toxin Weapons Convention
Biological Warfare
Biological Warfare, Advanced Diagnostics
Biological Weapons, Genetic Identification
CDC (United States Centers for Disease Control and Prevention)