Product Code Database
Poxviridae is a family of double-stranded DNA viruses. and serve as natural hosts. The family contains 22 genera that are assigned to two subfamilies: Chordopoxvirinae and Entomopoxvirinae. Entomopoxvirinae infect insects and Chordopoxvirinae infect vertebrates. Diseases associated with this family include smallpox.
Four genera of poxviruses can infect humans: Orthopoxvirus, Parapoxvirus, Yatapoxvirus, Molluscipoxvirus. Orthopoxvirus: smallpox virus (variola), vaccinia virus, cowpox virus, Mpox virus; Parapoxvirus: orf virus, pseudocowpox, bovine papular stomatitis virus; Yatapoxvirus: tanapox virus, yaba monkey tumor virus; Molluscipoxvirus: molluscum contagiosum virus (MCV). The most common are vaccinia (seen on the Indian subcontinent) and molluscum contagiosum, but Mpox infections are rising (seen in west and central African rainforest countries). The similarly named disease chickenpox is not a true poxvirus and is caused by the herpesvirus, varicella zoster. Parapoxvirus and orthopoxvirus genera are zoonotic.
A century after Edward Jenner showed that the less potent cowpox could be used to effectively vaccinate against the more deadly smallpox, a worldwide effort to vaccinate everyone against smallpox began with the ultimate goal to rid the world of the plague-like epidemic. The last case of endemic smallpox occurred in Somalia in 1977. Extensive searches over two years detected no further cases, and in 1979 the World Health Organization (WHO) declared the disease officially eradicated.
In 1986, all virus samples were destroyed or transferred to two approved WHO reference labs: at the headquarters of the federal Centers for Disease Control and Prevention (the C.D.C.) in Atlanta, Georgia (the United States) and at the Institute of Virus Preparations in Moscow. After the September 11 attacks in 2001, the American and UK governments have had increased concern over the use of smallpox, or a smallpox-like disease, in bioterrorism. However, several poxviruses including vaccinia virus, myxoma virus, tanapox virus and raccoon pox virus are currently being investigated for their therapeutic potential in various human cancers in preclinical and clinical studies.
The GC-content of family member genomes differ considerably. Avipoxvirus, capripoxvirus, cervidpoxvirus, orthopoxvirus, suipoxvirus, yatapoxvirus and one Entomopox genus (Betaentomopoxvirus) along with several other unclassified Entomopoxviruses have a low G+C content while others - Molluscipoxvirus, Orthopoxvirus, Parapoxvirus and some unclassified Chordopoxvirus - have a relatively high G+C content. The reasons for these differences are not known.
The replication of poxvirus is unusual for a virus with double-stranded DNA genome because it occurs in the cytoplasm,. although this is typical of other large DNA viruses. Poxvirus encodes its own machinery for genome transcription, a DNA dependent RNA polymerase, which makes replication in the cytoplasm possible. Most double-stranded DNA viruses require the host cell's DNA-dependent RNA polymerase to perform transcription. These host polymerases are found in the cell nucleus, and therefore most double-stranded DNA viruses carry out a part of their infection cycle within the host cell's nucleus.
The intermediate phase of replication is critical because, on that stage, the virus affects the host's normal function and modifies it more optimally to itself. For example, the virus can inhibit host apoptosis and block the antiviral state. On the replication, poxviruses have their enzymes for example vaccinia virus has decapping enzymes D9 and D10. Decapping enzymes that belong to the Nudix hydrolase superfamily those it used to remove mRNA 5'cap from viral and host mRNA. By removing 5'cap from the mRNA the virus reduces the accumulation of viral dsRNA and inhibit immune response.
Based on the genome organisation and DNA replication mechanism a phylogenetic relationships may exist between the rudiviruses ( Rudiviridae) and the large eukaryal DNA viruses: the African swine fever virus ( Asfarviridae), Chlorella viruses ( Phycodnaviridae) and poxviruses ( Poxviridae).
The mutation rate in poxvirus genomes has been estimated to be 0.9–1.2 x 10−6 substitutions per site per year.Babkin IV, Shchelkunov SN (2006) The time scale in poxvirus evolution. Mol Biol (Mosk) 40(1):20-24 A second estimate puts this rate at 0.5–7 × 10−6 nucleotide substitutions per site per year. A third estimate places the rate at 4–6 × 10−6.
The last common ancestor of the extant poxviruses that infect vertebrates existed . The genus Avipoxvirus diverged from the ancestor 249 ± 69 thousand years ago. The ancestor of the genus Orthopoxvirus was next to diverge from the other clades at . A second estimate of this divergence time places this event at 166,000 ± 43,000 years ago. The division of the Orthopoxvirus into the extant genera occurred ~14,000 years ago. The genus Leporipoxvirus diverged ~137,000 ± 35,000 years ago. This was followed by the ancestor of the genus Yatapoxvirus. The last common ancestor of the Capripoxvirus and Suipoxvirus diverged 111,000 ± 29,000 years ago.
An isolate from a fish – salmon gill poxvirus – appears to be the earliest branch in the Chordopoxvirinae. A new systematic has been proposed recently after findings of a new squirrel poxvirus in Berlin, Germany.(for systematic see figure 2)
A second estimate has placed the separation of variola from Taterapox at 3000–4000 years ago. This is consistent with archaeological and historical evidence regarding the appearance of smallpox as a human disease which suggests a relatively recent origin. However, if the mutation rate is assumed to be similar to that of the the divergence date between variola from Taterapox has been estimated to be 50,000 years ago. While this is consistent with the other published estimates it suggests that the archaeological and historical evidence is very incomplete. Better estimates of mutation rates in these viruses are needed.
The following subfamilies and genera are recognized (- virinae denotes subfamily and - virus denotes genus):
Subfamily: Chordopoxvirinae
Subfamily: Entomopoxvirinae
Vaccinia contains three classes of genes: early, intermediate and late. These genes are transcribed by viral RNA polymerase and associated transcription factors. Vaccinia replicates its genome in the cytoplasm of infected cells, and after late-stage gene expression undergoes virion morphogenesis, which produces intracellular mature virions contained within an envelope membrane. The origin of the envelope membrane is still unknown. The intracellular mature virions are then transported to the Golgi apparatus where it is wrapped with an additional two membranes, becoming the intracellular enveloped virus. This is transported along cytoskeletal microtubules to reach the cell periphery, where it fuses with the plasma membrane to become the cell-associated enveloped virus. This triggers actin tails on cell surfaces or is released as external enveloped virion.
Taxonomy
The species in the subfamily Chordopoxvirinae infect and those in the subfamily Entomopoxvirinae infect .
Vaccinia virus
The prototypical poxvirus is vaccinia virus, known for its role in the eradication of smallpox. The vaccinia virus is an effective tool for foreign protein expression, as it elicits a strong host immune-response. The vaccinia virus enters cells primarily by cell fusion, although currently the receptor responsible is unknown.
See also
External links
|
|
