Poxviridae

Baltimore Classification

Higher order taxa

root; Viruses; dsDNA viruses, no RNA stage; Poxviridae

Genera

Avipoxvirus, Capripoxvirus, Orthopoxvirus (examples)

Description and Significance

Poxviruses have been relegated to the position of relatively unimportant human pathogens after the global eradication of small pox.

Poxviruses are the largest viruses known. They are very easy to isolate and can be grown in a variety of cell cultures. They produce pocks on the chick chorioallantoic membrane (CAM). These pocks are characteristic, giving their name to all forms of infectious disease "a dose of the pox".

Genome Structure

The genome of the poxvirus is unsegmented and contains a single molecule of linear double-stranded DNA. The complete genome is 130000-375000 nucleotides long. The genome has a guanine-cytosine of 35-64% but only 20% for Entomopoxviruses. The genome has terminally redundant sequences that have reiterated inverted terminal sequences which are tandemly repeated. The genome sequence is repeated at both ends. The double-stranded DNA is covalently bonded and is cross-linked at both ends. (source ICTV dB Descriptions)

Virion Structure of a Poxvirus

The virions of poxviruses consist of a surface membrane, a core, and lateral bodies, or a surface membrane, a core and lateral bodies. They may or may not have an envelope. They produce extracellular and intracellular particles during their life cycle and can occur in two phenotypes. They may be enveloped during their extracellular phase. Extracellular virions intiate the infection. The virus may be sequestered within inclusion bodies that are not occluded and typically contain one nucleocapsid. The virion capsid is enveloped. The virions are generally ovoid and brick shaped, or phlemorphic. The ovoid virion is 140-260nm in diameter, 140-260nm in height and220-450nm in length while the pleomorphic virion is 160-190nm in diameter and 250-330nm in length.The virion is composed of an external coat containing lipid and tubular or globular protein structures enclosing one or two lateral bodies and a core, which contains the genome, displaying tubular units, or globular units, or regular spiral filaments. The core is unilaterally concave, or is biconcave, or is cylindrical with one lateral body, or two lateral bodies. Lateral bodies are usually lens-shaped and nested between the core membrane, or between the surface membrane. (source ICTV dB Descriptions)

Reproductive Cycle of a Poxvirus in a Host Cell

The replication of the poxvirus occurs in the cytoplasm. The virus is suficiently complex and has acquired all the functions necessary for genome replication. Although the cell contributes to the process, it is not clear what exactly the cell does: poxvirus gene expression and genome replication occur in enucleated cells, but maturation is blocked.

The receptors for poxvirus repliation are not know yet, but there are probably more than one on different cell types. The penetration is complex ad probably involves more than one mechanism. Two stages of uncoating take place. The outer membrane is removed as the particle enters the cell and in the cytoplasm, the particle is further uncoated and the core passes into the cytoplasm. Gene expression is carried out by viral enzymes associated with the core and is divided into two phases: early genes and late genes. Early genes are expressed before genome replication while late genes are expressed after genome replication and the late promoters are dependent on DNA replication for activity. The gene expression of poxviruses has been studied in detail because of the interest in the use of Vaccinia virus as a vector for the expression of heterologous genes.

The genome replication of the the poxvirus is believed to involve self-priming, leading to the formation of high m.w. concatemers that are isolated from infected cells which are subsequently cleaved and repaired to make virus genomes. Thymidine kinase and many other virus-encoded enzymes involved in replication offer potential targets for chemotheraputic agents.

The assembly occurs in the cytoskeleton. The events involved in putting together such a complex particle are not clearly understood yet, but probably involve interactions with the cytoskeleton, for example actin-binding proteins. Inclusions are formed in the cytoplasm which mature into virus particles. Actin 'comet tails' are formed and they shoot IEV through the cytoplasm to the cell surface, and possibly into adjacent cells. This movement has been timed and found to be 3µm/min. This may be instrumental in providing an alternate mechanism for cell to cell transmission. The relication of this large, complex virus is rather quick.

Rahima Banu, the last person with the naturally-occuring case of smallpox, is pictured here in 1975. From CDC; Courtesy World Health Organization; Stanley O. Foster M.D., M.P.H.

Viral Ecology & Pathology

The threats posed by the poxvirus have been effectively dealt with, leading to the eradication of the diseases caused by the virus.

Smallpox had already been eradicated from most countries in Europe and the US by 1940s but it still posed a serious threat in the Indian subcontinent and much of Africa in the 1960s. The World Health Organization (WHO) decided to take strong actions for the eradication of the disease and listed smallpox on the top of the list for eradication in 1967. The WHO smallpox eradication unit was set up in the same year.

After years of effort and investment into the eradication of smallpox, the last cases of variola major occured in the Indian subcontinent in 1975 while the last case of variola minor occured in Somalia in 1977. The last cases of smallpox occured in a Birmigam laboratory in 1979. Smallpox had been fought, and fought successfully.

Smallpox has been eradicated globally but there are concerns about the potential use of variola virus as a weapon of terror. As a result, destruction of the last official remaining smallpox stocks held in Russia and USA has now been postponed indefinitely. The possibility of the emerging or re-emerging of variola, monkeypox, camelpox, taterapox or any other orthopoxvirus as a threat to human health increases as the proportion of the world population that is immunologically naïve for orthopoxviruses increases. The possibility of rat to human transmission of cowpox infection, or other forms of OVPs jumping species and adapting to mankind, increases because of the parallel increase in immunosuppression due to AIDS. These possibilities justify the retention of adequate stocks of vaccinia, which can be used as vaccine, to combat poxvirus infections.

It is also unclear whether one single difference, a few differences or all differences between the genomes of viruses such as camelpox and smallpox are responsible for the inability of camelpox to cause human diseases. Hence, genetic modification of camelpox to delete genes that are present in camelpox but absent in smallpox might be higly dangerous. Genetic changes to cowpox could trigger reactions that might make humans susceptible to cowpox. Poxviruses could still pose serious threats to humans.

References

Stanford University: Poxviridae

The Big Picture Book of Viruses: Poxviridae

ICTV dB Descriptions