Vaccinia
Vaccinia virus (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family.[2] It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250 nm, with a mass of approximately 5–10 fg.[3] The vaccinia virus is the source of the modern smallpox vaccine, which the World Health Organization (WHO) used to eradicate smallpox in a global vaccination campaign in 1958–1977. Although smallpox no longer exists in the wild, vaccinia virus is still studied widely by scientists as a tool for gene therapy and genetic engineering.
This article is about the virus related to smallpox vaccines. For the plant genus, see Vaccinium.Smallpox had been an endemic human disease that had a 30% fatality rate. In 1796, the British doctor Edward Jenner proved that an infection with the relatively mild cowpox virus would also confer immunity to the deadly smallpox. Jenner referred to cowpox as variolae vaccinae (smallpox of the cow). However, the origins of the smallpox vaccine became murky over time,[4] especially after Louis Pasteur developed laboratory techniques for creating vaccines in the 19th century. Allan Watt Downie demonstrated in 1939 that the modern smallpox vaccine was serologically distinct from cowpox,[5] and vaccinia was subsequently recognized as a separate viral species. Whole-genome sequencing has revealed that vaccinia is most closely related to horsepox, and the cowpox strains found in Great Britain are the least closely related to vaccinia.[6]
In addition to the morbidity of uncomplicated primary vaccination, transfer of infection to other sites by scratching, and post-vaccinial encephalitis, other complications of vaccinia infections may be divided into the following types:[7]: 391
Origin[edit]
Vaccinia virus is closely related to the virus that causes cowpox; historically the two were often considered to be one and the same.[8] 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.[9] The most common notion is that vaccinia virus, cowpox virus, and variola virus (the causative agent of smallpox) were all derived from a common ancestral virus. There is also speculation that vaccinia virus was originally isolated from horses,[8] and analysis of DNA from an early (1902) sample of smallpox vaccine showed that it was 99.7% similar to horsepox virus.[10]
Virology[edit]
Poxviruses are unique among DNA viruses because they replicate only in the cytoplasm of the host cell, outside of the nucleus.[11] Therefore, the large genome is required for encoding various enzymes and proteins involved in viral DNA replication and gene transcription. During its replication cycle, VV produces four infectious forms which differ in their outer membranes: intracellular mature virion (IMV), the intracellular enveloped virion (IEV), the cell-associated enveloped virion (CEV) and the extracellular enveloped virion (EEV).[12] Although the issue remains contentious, the prevailing view is that the IMV consists of a single lipoprotein membrane, while the CEV and EEV are both surrounded by two membrane layers and the IEV has three envelopes. The IMV is the most abundant infectious form and is thought to be responsible for spread between hosts. On the other hand, the CEV is believed to play a role in cell-to-cell spread and the EEV is thought to be important for long range dissemination within the host organism.
Multiplicity reactivation[edit]
Vaccinia virus is able to undergo multiplicity reactivation (MR).[13] MR is the process by which two, or more, virus genomes containing otherwise lethal damage interact within an infected cell to form a viable virus genome. Abel[13] found that vaccinia viruses exposed to doses of UV light sufficient to prevent progeny formation when single virus particles infected host chick embryo cells, could still produce viable progeny viruses when host cells were infected by two or more of these inactivated viruses; that is, MR could occur. Kim and Sharp demonstrated MR of vaccinia virus after treatment with UV-light,[14] nitrogen mustard,[15] and X-rays or gamma rays.[16] Michod et al.[17] reviewed numerous examples of MR in different viruses, and suggested that MR is a common form of sexual interaction in viruses that provides the advantage of recombinational repair of genome damages.
Vaccinia contains within its genome genes for several proteins that give the virus resistance to interferons:
This is a list of some of the well-characterized vaccinia strains used for research and vaccination.