Yellow fever
Smallpox Virus
Content
Smallpox, one of the biggest killers in history, is caused by a virus called variola. Variola causes a distinctive rash and is often lethal. The name variola comes from the Latin word for "spotted" and refers to the raised bumps that appear on the face and body of infected individuals. Although similar in name and in the formation of a rash, blisters, and scabs, variola belongs to a different virus family than the virus that causes the common childhood illness chicken pox. Variola is a member of the Poxvirus family of viruses. A close relative of variola within the Poxvirus family, called vaccinia, does not cause smallpox and is used as a vaccine for smallpox (in fact, the word vaccine comes from vaccinia virus). Vaccinia is also used in the laboratory to study this type of virus, because it is less hazardous to work with than the smallpox virus.
A virus related to variola called monkeypox virus recently made headlines when an outbreak occurred in the Midwestern region of the United States in 2003. This disease, also characterized by a rash and blisters, was the first monkeypox outbreak in the Western Hemisphere. Monkeypox virus sickened about 70 people. The cause was traced to prairie dogs that had been infected by imported African rodents at a pet distribution center. Fortunately, this disease was not as deadly as smallpox.
People generally become infected with the smallpox virus by breathing in virus droplets following exposure to infected individuals or by direct contact with infected fluids or contaminated objects. An unusual property of the smallpox virus is that it only infects humans and not animals and insects (this property was instrumental in the eradication of smallpox). After exposure to the virus, it usually takes one to two weeks before a person becomes ill and a rash and fever develop. At this point, the person is highly contagious and remains contagious until all scabs fall off after about three weeks. About 30% of infected people die from smallpox infection. People who recover from the infection are often left with permanent scars and sometimes blindness.
By some estimates, smallpox has been responsible for more deaths over the centuries than all other infectious diseases combined. A worldwide immunization program was instituted decades ago and has led to the elimination of smallpox as a human health threat. This has been one of the greatest success stories in medicine. In the United States, the last confirmed case of smallpox occurred in 1949, and worldwide the last recorded case of naturally occurring smallpox occurred in Somalia in 1977. In 1980, the World Health Organization formally declared that smallpox had been eradicated. There are currently only two official laboratory stockpiles of the smallpox virus in the world – one housed at the Centers for Disease Control and Prevention in Atlanta and the other at a research facility in Russia.
Deadly Diseases
Of all the diseases ever suffered by humans, smallpox is the only one to be completely eradicated from the face of the Earth. The few known remaining samples are under heavy guard in research labs in Russia and the United States.
The campaign to eradicate smallpox ended in 1980 and is one of the greatest triumphs of global public health. In that year, the World Health Organization announced that the disease known medically as variola major had been eliminated in its last pockets of infection, India, Bangladesh, and Africa.
In its natural form, smallpox was transmitted from person to person by air through tiny droplets of saliva, and thus found particularly fertile territory in crowded cities and along trade and travel routes. The disease began with high fever and body aches. The infected person was most contagious when a rash appeared. But the hallmark of smallpox was the pus-filled swellings of the skin that left telltale scars on those fortunate enough to survive. Many victims, however, lost their sight.
Historically, 30 percent of cases progressed to death. The end was often painful as the skin lesions spread into every bodily opening, including the mouth and eyes. When these lesions blackened and peeled off, they emitted a sweet and pungent odor known as the "smallpox smell."
The disease originated more than 3,000 years ago in Africa or China and became epidemic in Europe during the Middle Ages. The virus was so prevalent and lethal that in some societies, parents didn't name their children until they had survived a bout with the virus. Smallpox was the single deadliest disease during the 18th century, striking commoners and royalty alike. Luis I of Spain (1707-1724), Peter II of Russia (1715-1730), and Louis XV of France (1710-1774) all succumbed to the disease. In London, one-third of the population carried the pockmark scars from the disease.
Smallpox came to the New World in the late 1400s and early 1500s, decimating native populations in the West Indies and continental Americas. During the French and Indian War (1754-1763), the British intentionally gave smallpox-contaminated blankets to the Indians, resulting in an epidemic with a 50 percent mortality rate.
The story of humankind's triumph over the disease gained momentum with the experiments of an English country doctor, Edward Jenner. In 1796 he made the crucial observation that farmhands and dairy maids who contracted cowpox from cows never came down with the similar but more virulent smallpox. He reasoned that inducing a mild infection of cowpox in people might protect them from getting smallpox.
In what would today be considered an unethical experiment, Jenner tested his theory on an 8-year-old boy by introducing into his skin pus from a woman infected with cowpox. Six weeks later he made two incisions in the boy's arm and inserted smallpox pus. The boy did not come down with the disease. Jenner called his procedure a vaccination, from the Latin vacca, for "cow."
During the next two centuries, vaccinations worldwide helped reduce the incidence of smallpox. The disease was susceptible to eradication because it is a uniquely human disease with no known reservoirs in the animal or insect worlds. The last person naturally infected with smallpox was a hospital cook in Somalia in 1977. Once a routine vaccination for children in America, the practice ended with the eradication of the disease in 1980.
Unfortunately, the fear of smallpox remains palpable. Terrorist attacks in the 21st century have raised concerns that some of the research stockpile of the smallpox virus may have been sold to nations or groups who might use it as a biological weapon. Under optimum conditions, the fragile smallpox virus could survive 24 hours after being sprayed in aerosol form. Traces of the virus would be gone by the time symptoms of the disease appeared in people 10 to 12 days later.
The United States government has responded with a nationwide preparedness plan, with enough vaccine stored to inoculate the entire American population. For this plan to be effective, however, it would be critical to vaccinate promptly anyone who had come into contact with an infected person. The Centers for Disease Control has emergency "Push-Pak" supplies that can be flown quickly to any part of the country.
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Poxvirus Tropism
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Spehner, D., Gillard, S., Drillien, R. & Kirn, A. A cowpox virus gene required for multiplication in Chinese hamster ovary cells. J. Virol. 62, 1297–1304 (1988). Another classic paper showing that a specific gene, CHOhr (or CP77), is required for the replication of cowpox virus in CHO cells.
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Chen, W., Drillien, R., Spehner, D. & Buller, R. M. L. Restricted replication of ectromelia virus in cell culture correlates with mutation in virus-encoded host range genes. Virology 187, 433–442 (1992).
Ramsey-Ewing, A. & Moss, B. Restriction of vaccinia virus replication in CHO cells occurs at the stage of viral intermediate protein synthesis. Virology 206, 984–993 (1995).
Ink, B. S., Gilbert, C. S. & Evans, G. I. Delay of vaccinia virus-induced apoptosis in nonpermissive Chinese hamster ovary cells by the cowpox virus CHOhr and adenovirus E1B 19K genes. J. Virol. 69, 661–668 (1995).
Hsiao, J. -C., Chung, C. -S., Drillien, R. & Chang, W. The cowpox virus host range gene, CP77, affects phosphorylation of eIF2 Ī± and vaccinia viral translation in apoptotic HeLa cells. Virology 329, 199–212 (2004).
Ramsey-Ewing, A. L. & Moss, B. Complementation of a vaccinia virus host-range K1L gene deletion by the nonhomologous CP77 gene. Virology 222, 75–86 (1996).