Poxviridae (Anglo-Saxon "pock", meaning pustule) is a virus family that infects both vertebrates and invertebrates. Throughout human history, Poxviruses have held great clinical significance. Perhaps the most famous of these viruses is variola (Latin, meaning “spotted”), more commonly known as smallpox. According to estimates given by the World Health Organization, 300-500 million deaths resulted from smallpox alone in the 20th century. While humans serve as the natural reservoir for several poxviruses (including smallpox), animals frequently serve as the reservoir for human infections through the process of zoonosis.
The study of poxviruses has yielded important developments in the field of virology. Indeed, the family boasts the first successful vaccine ever created - the smallpox vaccine, created by Edward Jenner in 1798. The implementation of this vaccine also led to the
first successful viral eradication effort.
Through vaccination, careful monitoring, and public health campaigns around the world, the virus was eliminated from the natural world in 1977.
910: the first medical report on smallpox, Treatise on Smallpox and Measles, was published by the Arabian scholar Rhazes
1520: introduction of smallpox to the New World via slave ships
1721: the practice of variolation, invented a few thousand years earlier, was introduced in England and subsequently became widespread. The practice involves infecting individuals through an alternate route of transmission (skin-skin contact vs. respiratory) by rubbing pustule matter on the skin of normal individuals, resulting in a mild infection.
1798: Edward Jenner publishes An Inquiry into the Causes and Effects of the
Variolae Vaccinae; A Disease Discovered in Some of the Western Countries of England, particularly Gloucestershire, and Known by the Name of the Cow Pox, a paper that recognizes the immunity conferred against smallpox from cowpox infection, effectively creating the first-ever vaccine.
1802: The safety and effectiveness of the smallpox vaccine was confirmed by the American physician Benjamin Waterhouse
1949: The last known case of smallpox in the United States (Rio Grande Valley, Texas)
1958: Monkeypox discovered in monkeys, and subsequently found to exist in African rodents
1966: The Worldwide Smallpox Eradication Programme was established by the World Health Assembly
1970: Monkeypox reported in humans
1977: Ali Maalin becomes the last person to naturally contract variola (variola minor)in the world in Somalia. Depicted on right. Retrieved from vaccinenewsdaily.com
1978: Janet Parker and her mother die of smallpox, as a result of a laboratory accident at the University of Birmingham Medical School in England under Professor Henry Bedson
1979: Eradication of smallpox declared by the World Health Organization.
1996: Recommendation by the World Health Assembly for the remaining laboratory stocks of smallpox to be destroyed
2003: Outbreak of monkeypox reported in the Midwest of the United States; was found to be attributed to prairie dogs
2014: The World Health Organization postpones destruction of remaining laboratory stocks of smallpox; will reconvene in 2017 to discuss the matter again
Poxviruses share several features that characterize them as a member of Poxviridae: a monopartite, linear genome consisting of double-stranded DNA, a linear genome, a “complex” morphology composed of a biconcave core with an ovoid or brick-shaped nucleocapsid, and an extremely large size relative to other human viruses (200-350nm). Poxviridae is further subdivided into two subfamilies: chordopoxvirinae (infects humans and other animals) and entomopoxvirinae (infects arthropods).
Interestingly enough, Poxviridae is the only virus family that contains both non-enveloped and enveloped members, prompting some scholars to argue for the subdivision of Poxviridae as two distinct viral families. Under the current taxonomic classification system however, two of the genuses in the family are used to distinguish the presence of an envelope in poxviruses: orthopoxviruses (enveloped) and parapoxviruses (non-enveloped). Other genuses in the family include: avipoxvirus, capripoxvirus, leporipoxvirus, suipoxvirus, molluscipoxvirus, and yatapoxvirus.
The process of viral replication in poxviruses begins with viral attachment to surface cell receptors, followed by entry of the virus via endocytosis by the host cell. The cell tropism for poxviruses are typically epidermal cells. Once in the host cell, the virus uncoats its viral DNA in the cytoplasm, and begins the process of replication in viral replication factories called virosomes.
Poxviruses are the only DNA virus that replicate in the cytoplasm and the only DNA virus with its own transcriptional machinery. As a result, they can direct replication soon after cell entry, but also must encode a significant amount of information in their genome. In all, the virus encodes more than 100 genes, including the enzymes DNA polymerase and DNA-dependent RNA transcriptase. Enzymes like poly(A) polymerase and mRNA capping enzymes further aid in viral replication by equipping the virus with a poly(A) tail and an mRNA cap in preparation for translation.
Poxviruses have three kinetic classes that allow transcription of certain genes to be prioritized and transcribed sequentially. The early class allows for transcription of several critical genes, including the uncoating enzyme, critical for the start of viral translation.
Following transcription, translation of the transcript takes place in the host cell cytoplasm, where viruses assemble in viral “factories”. Once assembled, poxviruses facilitate release in one of two ways. Enveloped poxviruses bud from the host cell, while non-enveloped viruses trigger cell lysis. Replication depicted on right. Retrieved from Nature.
Poxviruses are generally transmitted via respiratory secretions or skin-skin contact.
Poxviruses for which humans are the natural reservoir
1. Variola (Orthopoxvirus)Variola actually exists in two forms: variola major and variola minor (alastrim). Variola major is the more severe form of
smallpox, with a mortality rate of 10-20% compared to ~1% in variola minor. Thanks to eradication efforts in the 1960s and 1970s, the virus is no longer naturally found in the world, and can only be found in stocks kept in laboratories in the U.S.
(CDC in Atlanta) and Russia (Vector in Koltsovo).
Symptoms: Pustules, high fever, chills, vomiting, can cause blindness if lesions occur on eyes.
Clinical Presentation of smallpox
Retrieved from techtimes.com
Prevention: Vaccination with the live-attenuated vaccinia vaccine, derived from vaccinia (cowpox)
Treatment: 1. Cidofovir, a nucleotide analog that inhibits proper viral replication 2. CMX-001, an inhibitor of viral polymerase 3. Tecovirament, a drug that prevents viral egress from the host cell.
Drug Profile: Cidofovir
2. Molluscum Contagiosum (Molluscipoxvirus)
Molluscum Contagiosum is a poxvirus that is transmitted by direct skin contact or sexual contact that results in skin-colored papules on the skin. It is a mild condition, and symptoms typically resolve themselves within a few days-weeks. While the immune system is usually able to fight off the virus before symptoms develop, HIV infected individuals as well as other immunocompromised individuals show higher rates of disease.
Symptoms: skin-colored, smooth, waxy papules (2-10mm diameter)
Prevention: abstinence, safe sex, avoiding direct contact with those presenting papules
Treatment: liquid nitrogen on papules
Table 1 Poxviruses for which humans are not the natural reservoir (zoonoses)
*Varicella zoster virus, more commonly known as chickenpox, is actually a misnomer, as a member of Herpesviridae
Of particular note above is monkeypox, an emerging virus. First detected in African monkeys in 1958, the virus has been responsible for several human outbreaks. In 1970, the first human case of monkeypox was reported in Zaire. Sustained human to human transmission occurred for the first time in the Republic of Congo in 2003, and an outbreak in the United States occurred in 2003. The suspected culprit behind the U.S. outbreak was the Gambian giant rate, which was believed to have infected the victim’s prairie dog.
10 THINGS TO REMEMBER ABOUT POXVIRIDAE
Andrew Duong | Stanford University | Humans and Viruses 2015 | March 18th, 2015