Poxviridae

Poxviridae

History of poxviridae
Smallpox has figured in two landmark events in the history of medical science and public health. The first documented modern instance of the use of active immunization to confer immunity against disease occurred in 1796 when the British physician Edward Jenner inoculated a person with cowpox virus (also an Orthopoxvirus) to produce protection against smallpox. The terms vaccine and vaccinate derive from vacca, Latin for “cow.” Nearly two centuries after Jenner's achievement, an international vaccination campaign made smallpox the first major disease to be completely eradicated by human action. Smallpox did not cease to be a potential public health concern, however, since there remained the possibility that smallpox virus taken from undestroyed stocks of the virus could be used by terrorists or a belligerent government as a deadly biological weapon.

How Edward Jenner discovered the vaccination for poxviridae

Edward Jenner was an English country doctor who pioneered vaccination. Jenner's discovery in 1796 that inoculation with cowpox gave immunity to smallpox was an immense medical breakthrough and has saved countless lives.

Jenner worked in a rural community and most of his patients were farmers or worked on farms with cattle. In the 18th century smallpox was a very common disease and was a major cause of death. The main treatment was by a method which had brought success to a Dutch physiologist Jan Ingenhaus and was brought to England in 1721 from Turkey by Lady Mary Wortly Montague. This method involved inoculating healthy people with substances from the pustules of those who had a mild case of the disease, but this often had fatal results.

In 1788 an epidemic of smallpox hit Gloucestershire and during this outbreak Jenner observed that those of his patients who worked with cattle and had come in contact with the much milder disease called cowpox never came down with smallpox. Jenner needed a way of showing that his theory actually worked. He was given the opportunity on the 14 May 1796, when a young milkmaid called Sarah Nelmes came to see him with sores on her hands like blisters. Jenner identified that she had caught cowpox from the cows she handled each day.

Jenner now had the opportunity to obtain the material try out his theories. He carefully extracted some liquid from her sores and then took some liquid from the sores of a patient with mild smallpox. He believed that if he could inject someone with cowpox, the germs from the cowpox would make the body able to defend itself against the dangerous smallpox germs which he would inject later.

He approached a local farmer called Phipps and asked him if he could inoculate his son James against smallpox. He explained to the farmer that if his theory was correct, James would never contract smallpox. Surprisingly, the farmer agreed. He made two small cuts on James's left arm. He then poured the liquid from Sarah's cowpox sores into the open wounds which he bandaged. James went down with cowpox but was not very ill. Six weeks later when James had recovered, Jenner vaccinated him again, this time with the smallpox virus. This was an extremely dangerous experiment. If James lived Jenner would have found a way of preventing smallpox. If James developed smallpox and died he would be a murderer. To Jenner's relief James did not catch smallpox. His experiment had worked.

In 1798 after carrying out further successful tests, he published his findings: An Inquiry into the Causes and Effects of the Variolae Vaccinae, a Disease Known by the Name of Cow Pox. Jenner called his idea " vaccination" from the word vaccinia which is latin for cowpox. Jenner also introduced the term virus.

Classification and Taxonomy

Pox viruses are the largest and most complex of all viruses. In fact, they are large enough, with a virion size of 220-350 x 115-260 nm, to be seen under a light microscope. They infect a wide range of hosts, and are divided into two subfamilies: Chordopoxvirinae and Entomopoxviridae. All human pox viruses are in the Chordopoxovirinae subfamily, and most of them belong to either the Orthopoxvirus (variola, vaccinia, cow pox) or the Parapoxvirus (Orf virus) genus. The chicken pox virus does not belong to this family. It is a herpesvirus.

• genome: double-stranded DNA, monopartite, linear, noninfectious; encodes over 100 genes, including DNA dependent RNA transcripase

• morphology: "complex", ovoid or brick-shaped nucleocapsid
• envelope: orthopox are enveloped, parapox are not
• replication: takes place in cytoplasm
• host range: host range varies by specific virus; zoonoses is common, but small pox only infects humans
• oncogenicity: may cause benign tumors

Replication
Occurs in the cytoplasm - the virus is sufficiently complex to have acquired all the functions necessary for genome replication. There is some contribution from the cell but it is not clear what this is - poxvirus gene expression and genome replication occur in enucleated cells, but maturation is blocked.

Characteristics and Prevention

The virus is commonly picked up by inhaling droplets from the mouth and nose of an infected person. It may also be transmitted through contact with material from the skin lesions that appear on an infected individual.

The incubation period for smallpox is between seven and 17 days following exposure, with the average being 12 days. The following are the most common symptoms of smallpox. However, each individual may experience symptoms differently. Symptoms may include:

• initial symptoms:
  - high fever
  - fatigue
  - head and back aches
• a distinct rash that presents with the following characteristics, most often, two to three days after exposure:
  - a rash starts with flat, red lesions, usually on the face, arms, and legs
  - lesions become pus-filled and start to crust over early in the second week
  - scabs form which then separate and fall off after three to four weeks

A person with smallpox is infectious from the first appearance of fever until all the scabs fall off. There are two chief forms of the disease, variola major and variola minor, and they result in similar lesions. Variola minor follows a milder course, with a fatality rate under 1 percent. Variola major kills an estimated 30 percent of those infected.

There is no specific treatment for smallpox. Administering smallpox vaccine to people soon after they are exposed to the virus, however, may prevent the disease from developing or at least ameliorate its effects. Researchers are exploring the potential use of antiviral drugs against smallpox.

Eradiction of Poxviridae
In 1967 the WHO launched a worldwide vaccination campaign against smallpox; at the time, some 10 to 15 million cases of the disease occurred each year, with more than 2 million deaths. By mid-1975, when all of India was declared free of smallpox, only a few cases were left in two countries, Bangladesh and Ethiopia. In 1979, after two years without a reported case of naturally occurring smallpox, a commission of scientists certified the disappearance of the disease from the earth. The WHO subsequently recommended that countries stop vaccinating against the disease and that laboratory stocks of the virus be destroyed. Underlining the importance of this last request was the death of an English woman in 1979 from smallpox contracted from a laboratory working with the virus. June 1999 was set as the deadline for the destruction of the two known remaining stocks of smallpox virus, kept in guarded freezers at the Centers for Disease Control and Prevention in Atlanta, Ga., and the Russian State Research Center of Virology and Biotechnology in Koltsovo, near Novosibirsk, Siberia. Some scientists, however, argued that the two official stocks should be preserved for research on the virus and on new vaccines and antiviral agents, a position that gained added force from the possibility that additional samples of the virus might exist elsewhere. The WHO accordingly changed the target date for destruction of the virus to 2002. In May 2002, reflecting heightened concerns over the possible use of bioweapons by political extremists, the WHO again put off the elimination of the official stocks.

Vaccination was almost universally adopted worldwide around 1800, but it took a major commitment from the WHO in 1965 to achieve eradication.Eradication of smallpox was possible for 3 reasons:

• There is no other reservoir for VV but man.
• VV causes only acute infections, from which the infected person either:
  - Dies
  - Recovers with life-long immunity.
• Vaccinia virus is an effective immunogen.

Smallpox as Biological Weapon
Smallpox was used as a biological weapon by Europeans in the Americas, whose indigenous inhabitants were particularly susceptible to the variola virus, since they lacked a history of exposure to it. In the 16th century the Spanish conquistador Francisco Pizarro reputedly gave smallpox-contaminated clothing to South American natives. In the 18th-century French and Indian War in North America, British commanders gave Native Americans blankets and other goods that had been used by smallpox victims; the ensuing death rates reportedly reached as high as 50 percent.
More recently, the virus has been identified as a particularly promising choice for a biological weapon for a variety of reasons, among them: it can be readily produced in a stable aerosol form, which facilitates distribution; fewer than one hundred virus particles may suffice to cause infection; the disease has a relatively short incubation period and is often fatal; and because smallpox was considered eradicated, huge numbers of people have not been vaccinated against it. Smallpox was among the diseases investigated by the Japanese Army's secret germ-warfare operation called Unit 731 that conducted tests on prisoners in Mongolia and China prior to and during World War II. The Soviet Union reportedly began large-scale production of smallpox virus around 1980, and it is possible that other countries have established secret smallpox stockpiles.

Incidents of mail-transmitted anthrax in late 2001 sharpened concern among public health specialists over the potential use of the smallpox virus as a terrorist weapon. The U.S. government consequently began vaccinating certain members of the armed forces against smallpox, launched a program to offer smallpox vaccinations to health-care providers and other individuals involved in the initial emergency response to an outbreak of the disease, and stockpiled enough vaccine to immunize the entire U.S. population in the event a smallpox emergency occurred.

References
http://www.stanford.edu/group/virus/pox/pox.html#Introduction
http://www.history.com/encyclopedia.do?vendorId=FWNE.fw..sm129900.a#FWNE.fw..sm129900.a
http://www.zephyrus.co.uk/edwardjenner.html
http://www.edward-jenner.com/vaccinations.html
http://freemasonry.bcy.ca/biography/jenner_e/jenner_e.html
http://www.microbiologybytes.com/virology/Poxviruses.html
http://www.umm.edu/bioterrorism/smallpox.htm
http://en.wikipedia.org/wiki/Smallpox