Poxviridae

TRANSMISSION ROUTE: Direct contact, inhalation

Definition

Poxviridae is a family of double-stranded DNA (deoxyribonucleic acid) viruses that comprises two subfamilies: Chordopoxvirinae and Entomopoxvirinae. All poxviruses that cause disease in humans belong to Chordopoxvirinae. Infamous members of this subfamily include variola virus, which causes smallpox, and vaccinia virus, which was used to create the vaccine against smallpox. Other human diseases caused by poxviruses are molluscum contagiosum, mpox (previously known as monkeypox), cowpox, milker’s nodes, orf, yabapox, and tanapox. All poxvirus infections in humans are associated with skin lesions. Smallpox and molluscum contagiosum occur only in humans; the others are animal diseases that are occasionally transmitted to humans.

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Natural Habitat and Features

Poxvirus family members are the largest and most complex of all viruses. With a length of 220 to 450 nm (nanometers) long, they are large enough to be seen under a light microscope. The virions are oval or brick-shaped, which differs considerably from the highly symmetrical structure of other viruses. A dumbbell-shaped core contains linear double-stranded DNA that is 130 to 375 kilobase pairs in length. The viral core is surrounded by a core wall and a phospholipid-bilayer envelope. As infectious viral particles exit the cell, they gain a second envelope.

Poxviruses bind to one of several types of cell surface receptors and enter the cell through endocytosis or by direct fusion of the viral envelope with the plasma membrane. Poxviruses replicate in the cytoplasm of the host cell rather than in the nucleus. This distinguishes them from other DNA viruses and requires that they carry their own enzymes for replication. The poxvirus capsid contains more than one hundred different types of proteins, including dozens of enzymes required for transcription and translation of the viral genome.

Pathogenicity and Clinical Significance

Human history has been shaped by the devastating effects of variola, the smallpox virus. Smallpox has determined the outcome of wars, toppled civilizations, and killed countless persons on multiple continents. Smallpox also holds a unique place in history as the first disease to be eradicated worldwide. The last known case of smallpox was in Somalia in 1977.

Variola virus was one of the most pathogenic viruses known. With a mortality rate of 30 to 50 percent, it killed 300 to 500 million people during its existence. Molluscum contagiosum virus is the only other poxvirus that is found worldwide. In contrast to variola, molluscum contagiosum virus is a trivial pathogen. It causes painless, benign skin lesions and is not associated with systemic illness. It is most common in children, and it also can be transmitted sexually.

All other members of the poxvirus family that cause disease in humans are animal viruses that are transmitted to humans. Human mpox, the only seriously pathogenic illness in this group, occurs in villages in the tropical rain forests of West Africa and Central Africa. According to the World Health Organization (WHO), mpox is transmitted to humans through physical contact with someone who is already infectious, through contaminated materials, or through infected animals. The symptoms of mpox are similar to those of a mild case of smallpox, with a mortality rate of 10 to 15 percent.

Three different poxviruses can be transmitted from cows to humans during milking. Vaccinia virus, cowpox virus, and milker’s nodule virus cause minor, localized infections, usually on the hands. Orf virus, which causes similar skin lesions, is acquired through direct contact with sheep or goats.

Yabapox and tanapox viruses occur only in tropical regions of Africa. Yabapox produces large, benign tumors and is transmitted to humans through monkeys. Tanapox is a somewhat common skin infection in regions of Kenya and the Democratic Republic of the Congo. Systemic illness lasts about four days, with symptoms that include fever, headache, and backache. Skin lesions heal within several weeks.

Drug Susceptibility

No pharmaceutical treatment exists for poxvirus infection. Nucleoside and nucleotide analogs have been investigated for use as anti-poxvirus agents. Vaccination remains the only weapon against smallpox. The smallpox vaccine also confers 85 percent protection against mpox virus.

Bibliography

De Clercq, Erik, and Johan Neyts. “Therapeutic Potential of Nucleoside/Nucleotide Analogues against Poxvirus Infections.” Reviews in Medical Virology 14 (2004): 289-300.

Madigan, Michael T., and John M. Martinko. Brock Biology of Microorganisms. 12th ed. Upper Saddle River, N.J.: Pearson/Prentice Hall, 2010.

Mercer, Andrew, Axel Schmidt, and Olaf Weber, eds. Poxviruses. Basel, Switzerland: Birkhauser, 2007.

"Mpox (monkeypox)." World Health Organization, 18 Apr. 2023, www.who.int/news-room/fact-sheets/detail/monkeypox. Accessed 24 May 2024.

Rimoin, Anne W., et al. “Major Increase in Human Monkeypox Incidence Thirty Years After Smallpox Vaccination Campaigns Cease in the Democratic Republic of Congo.” Proceedings of the National Academy of Sciences 107 (2010): 37.