II.

Cause

The scientific name for smallpox is variola, from a Latin word meaning 'spotted.” Scientists recognize two main forms of smallpox caused by related subspecies of viruses. Variola major is the more serious form of the disease, believed to kill anywhere from 20 to 40 percent of those infected. Variola minor, on the other hand, produces milder symptoms and is fatal in around 1 percent of cases. In between the major and minor forms are a variety of intermediate strains. All forms of the disease, when not fatal, can leave survivors with permanent, disfiguring scars on the face and other areas. Smallpox can also cause blindness and, in the case of males, sterility.

The variola viruses belong to a virus group known collectively as orthopoxviruses, also referred to more simply as pox viruses—the largest viruses known. Smallpox viruses are shaped somewhat like bricks, measuring in size from 250 to 300 nanometers across—almost big enough to be visible with an ordinary light microscope. Inside a variola virus, within an outer shell made up of scores of proteins, lies a coiled strand of deoxyribonucleic acid (DNA), the virus’s genetic material.

Smallpox is primarily spread via airborne, virus-laden droplets exhaled by an infected person. Prolonged contact is not required. In one recorded case, for example, an infected person in a shop passed the virus to two visitors who had made a brief stop in the shop. In a laboratory accident in 1978 in the United Kingdom, a bit of mistakenly released virus traveled via an air duct from one floor of the lab to another, fatally infecting a medical photographer. The virus can also survive for extended periods in dust, clothing, bedding, and other objects, providing still more opportunities for infection.

The smallpox virus typically enters the body through the mouth or nose, ultimately invading the cells of the lymph nodes and the lungs. Once inside a cell, the smallpox virus employs the same stealthy act of hijacking employed by all viruses, commandeering the infected cell's own genetic machinery to make as many as 100,000 copies of itself. Some of these viruses instruct the host cell to send out finger-like tendrils that make contact with other cells. It is through these extensions that new cells become infected with virus particles and the viral replication process repeats. After the virus has used a cell to replicate, it abandons the cell, leaving it to die.

Eventually smallpox virus particles circulate in the bloodstream—a condition known as viremia. The virus may then invade the liver, spleen, and other internal organs, but it shows a preference for the mucous membranes of the mouth and especially the epithelial cells of the skin. This viral invasion of the skin, in turn, leads to the painful, pus-filled lesions that are the hallmark of the disease. Meanwhile, throughout the body, infected and dying cells release toxins of their own that also contribute to illness.

In nonfatal cases, the body's immune system finally succeeds in defeating the infection by developing specialized antibodies that neutralize the smallpox virus. These antibodies continue to circulate in the bloodstream and provide the disease's one compensation: long-term immunity against further smallpox infection (see Immunization).