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Smallpox is an acute, highly contagious disease, which causes disfiguring and febrile rash-like illness, which has no known cure. According to some health experts, smallpox was responsible for more deaths than all other infectious diseases combined thus far in the world's history <ref name="Smith">Smith, K. “Smallpox. can we still learn from the journey to eradication?” Indian Journal Of Medicine.  137.5 (2013): 895-899.</ref>. The disease causes high morbidity and mortality and led to the deaths of approximately 500 million people in the 20th century alone. With so many people affected, in an intensive public health vaccination campaign was initiated by the World Health Organization (WHO) to eradicate smallpox as a human disease in the 1960’s. There were two forms of the disease worldwide: Variola major, the deadly disease, and Variola minor, a much milder form <ref name="Smallpox">“Smallpox.” Center for Disease Control and Prevention. CDC, n.d. Web. 28 Oct. 2015. <http://www.bt.cdc.gov/agent/smallpox/index.asp></ref>. Although naturally occurring smallpox no longer exists, there are concerns that the variola virus could be used as an agent of bioterrorism or biowarfare. As a result, it is critical to understand the molecular dynamics and virulence factors in order to prepare for a potential epidemic and to prevent the devastating consequences <ref name="Smallpox" /> .

Smallpox is caused by the Variola virus, a member of the genus Orthopoxvirus. It’s genome consists of a single, linear double-stranded DNA molecule made up of 186,102 base pairs <ref name="Shubhash">. There are 10 enzymes that regulate gene expression, as well as about 100 nucleoproteins involved in transcription of the DNA. The DNA and nucleoproteins are held within a biconcave (dumbbell-shaped) core with two lateral bodies on either side. The function of the lateral bodies is unknown. The outer surface of the variola virus consists of lipids and proteins that surround this core. The variola virus consists of 90% protein, 5% lipid, and 3% DNA (Shubhash and Parija, 2009).