Color enhanced Transmission Electron Microscope (TEM) of the Vaccinia virus. A member of the poxvirus family, it is very close to the smallpox virus. As a result, it is commonly used to make the vaccine against the smallpox. Vaccinia virus (VACV or VV) is a large, complex, enveloped virus with a linear, double-stranded DNA genome. Smallpox was the first disease to be widely prevented by vaccination due to pioneering work by Edward Jenner in the 18th century. Vaccinia virus is the active constituent of the vaccine that eradicated smallpox, making it the first human disease to be eradicated. Vaccinia virus is closely related to the virus that causes cowpox; historically the two were often considered to be one and the same. The precise origin of vaccinia virus is unknown due to the lack of record-keeping as the virus was repeatedly cultivated and passaged in research laboratories for many decades. The most common notion is that vaccinia virus, cowpox virus, and variola virus were all derived from a common ancestral virus. There is also speculation that vaccinia virus was originally isolated from horses. Poxviruses are unique among DNA viruses because they replicate only in the cytoplasm of the host cell, outside of the nucleus. Magnification: unknown.