Poxviruses are brick‐shaped, enveloped viruses, each containing a linear, double‐stranded DNA (deoxyribonucleic acid) genome of 134–365 kilobases (kb). Several family members, including variola, monkeypox, cowpox, vaccinia, orf and molluscum contagiosum viruses, cause disease in humans. Smallpox, which was caused by variola virus, was once responsible for the deaths of millions each year. In 1796, Jenner showed that inoculation of material from a cowpox lesion could protect against smallpox: vaccination had been introduced into medicine. Moreover, through the use of cowpox and vaccinia virus vaccines, the dread disease of smallpox was eradicated from the natural environment. Although variola virus, the principal poxvirus pathogen, is no longer a public health hazard, the poxviruses have continued to be the focus of intense study because they provide unique systems for investigation of mechanisms important in molecular biology, viral pathogenicity and immunity. Attenuated poxviruses now provide some of the most promising contemporary platforms for broad‐spectrum, live‐virus vaccines.

Key Concepts

  • Variola virus, which causes smallpox, is one of the most virulent human pathogens.
  • Variola virus was the first virus to be eradicated from the natural environment.
  • Jenner showed that infection with cowpox could protect against infection with smallpox.
  • Cowpox virus was the original vaccine, hence the name vaccine, from the Latin word vacca for cow.
  • The worldwide eradication of the disease of smallpox was achieved by immunisation with vaccines containing live vaccinia viruses (viruses similar to, but more attenuated than, cowpox virus).
  • Except for variola virus and molluscum contagiosum virus (MCV), most of the poxvirus diseases of humans are zoonoses (diseases transmitted to humans from animals).
  • Among viruses, the poxviruses are unusually independent of host cell functions, employing mainly viral enzymes for viral gene transcription and viral DNA replication in the cytoplasm of infected cells.
  • Poxviruses do not establish latent infections.
  • Poxviruses possess many accessory genes that are not required for virus replication in vitro, but which are advantageous for virus replication in vivo.
  • Most of the accessory proteins encoded by poxviruses of vertebrates interfere with either innate or adaptive immune responses.

Keywords: cowpox; vaccinia; smallpox; vaccines; viral replication; virus‐host interactions

Figure 1. The poxvirus replication cycle. The cowpox virus replication cycle is depicted diagrammatically progressing from left to right. The upper panel shows morphological features of replication: (1) attachment, fusion and entry of the virus particles, where the EV outer membrane is disrupted or the matrix of the ATI is solubilised to release an MV capable of attachment to and fusion with the plasma membrane; (2) the uncoating of the MV to generate the cores; (3) the formation of viroplasm in the viral factories or viral B‐type inclusions; (4) the morphogenetic pathway leading from crescents to the formation of immature virus particles (IVs) that may contain electron‐dense condensed regions; (5) transition of the IVs into the mature virions (MVs); (6) the MVs subsequently enter one of the three pathways, namely retention in the cytoplasm, conversion into MVs embedded within the A‐type inclusions (ATIs) or conversion into the wrapped virions (WVs) possessing two additional membrane layers. The WVs are transported to the plasma membrane on microtubules. At the cell periphery, the outermost membrane of the WV fuses with the plasma membrane to produce an EV on the outer surface of the cell. This particle is then propelled from the cell on the tips of generated by the formation of actin tails in the cytoplasm under the cell‐associated EV. The EVs are projected from live cells. The residual MVs in the cytoplasm and the ATIs containing embedded MVs are released on death and disintegration of the infected cell. The lower panel depicts the onset of the various stages of the replication cycle relative to the time of infection.
Figure 2. Intermediates in poxvirus morphogenesis. A transmission electron micrograph of a thin section through the cytoplasm of a cell infected with vaccinia virus showing several intermediate forms of the virus particle. Key: C, crescent; IV, immature virion; MV, mature virion and V, viroplasm (granular material containing viral DNA and proteins). The arrows indicate progressively more mature forms of virus particle. Note the characteristic dumbbell‐shaped core in the MV at the right‐hand edge of the figure. Electron micrograph courtesy of Dr Sara E Miller (Department of Pathology, Duke University Medical Centre).


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Further Reading

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Pickup, David J(Mar 2015) Poxviruses. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001083.pub3]