Orthopoxvirus

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Orthopoxvirus
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Varidnaviria
Kingdom: Bamfordvirae
Phylum: Nucleocytoviricota
Class: Pokkesviricetes
Order: Chitovirales
Family: Poxviridae
Subfamily: Chordopoxvirinae
Genus:Orthopoxvirus
Species

See text

Orthopoxvirus is a genus of viruses in the family Poxviridae and subfamily Chordopoxvirinae . Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated with this genus include smallpox, cowpox, horsepox, camelpox, and mpox. [1] [2] The most widely known member of the genus is Variola virus , which causes smallpox. It was eradicated globally by 1977, through the use of Vaccinia virus as a vaccine. The most recently described species is the Alaskapox virus , first isolated in 2015. [3]

Contents

Microbiology

Structure

Schematic drawing of (cross section) of Orthopoxvirus virions (one enveloped, one not) and structural proteins Poxprot.jpg
Schematic drawing of (cross section) of Orthopoxvirus virions (one enveloped, one not) and structural proteins

Orthopoxviruses are enveloped with brick-shaped geometries and virion dimensions around 200 nm wide and 250 nm long. [1]

Genome

Member viruses have linear double-stranded DNA genomes around 170–250 kb in length. [1]

Lifecycle

Orthopoxvirus replication cycle Poxviridae cycle.jpg
Orthopoxvirus replication cycle

Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment of the viral proteins to host glycosaminoglycans (GAGs), which mediate cellular endocytosis of the virus. Fusion of the viral envelope with the plasma membrane releases the viral core into the host cytoplasm. Expression of early-phase genes by viral RNA polymerase begins at 30 minutes after infection. The viral core is completely uncoated as early expression ends, releasing the viral genome into the cytoplasm. At this point, intermediate genes are expressed, triggering genomic DNA replication by the viral DNA polymerase about 100 minutes post-infection. Replication follows the DNA strand displacement model. Late genes are expressed from 140 min to 48 hours postinfection, producing all viral structural proteins. Assembly of progeny virions begins in cytoplasmic viral factories, producing a spherical immature particle. This virus particle matures into the brick-shaped intracellular mature virion, which can be released upon cell lysis, or can acquire a second membrane from the Golgi apparatus and bud as extracellular enveloped virions. In this latter case, the virion is transported to the plasma membrane via microtubules. [1]

Transmission

Natural hosts of orthopoxviruses are mammals and arthropods. Member viruses are transmitted by respiratory droplets, contact, and zoonosis. [1]

Distribution

Some orthopoxviruses, including the mpox, cowpox, and buffalopox viruses, have the ability to infect non-reservoir species. Others, such as ectromelia and camelpox viruses, are highly host-specific. Vaccinia virus, maintained in vaccine institutes and research laboratories, has a very wide host range. Vaccine-derived vaccinia has been found replicating in the wild in Brazil, where it has caused infections in rodents, cattle, and even humans. [4] Following the eradication of variola virus, camelpox has become one of the most economically important Orthopoxvirus infections, because many subsistence-level nomadic communities depend heavily on camels.[ citation needed ]

Taxonomy

The genus contains the following species: [2] [3]

Evolution

Among the path of evolution of the Orthopoxvirus species, many genes are truncated (but still functional), fragmented, or lost. Cowpox strains tend to have the most intact genes. Predicting the phylogeny by sequence or by gene content produces somewhat different results: [5]

Orthopoxvirus phylogeny
By sequenceBy gene content

Ectromelia virus

Cowpox virus, Germany and Brighton

Taterapox virus, Camelpox virus, Variola virus

Mpox virus

Cowpox virus, GRI strain

Vaccinia virus, including rabbitpox and horsepox

Some of the differences in the two trees are attributed to the procedure of passage in producing vaccinia strains. The Modified vaccinia Ankara strain in this regard has much gene loss related to in vitro passage, and horsepox being a vaccinia strain found in a natural outbreak has less. [5]

Infection in humans

Zoonoses

Following the eradication of the human-specific variola virus (smallpox), all human Orthopoxvirus infections are zoonoses. [6] Mpox occurs naturally only in Africa, particularly in the Democratic Republic of the Congo. [7] However, human and prairie dog cases have occurred in the US due to contact with animals imported from Ghana, [8] while in May 2022 an outbreak of mpox began spreading globally. Cowpox only occurs in Europe and adjacent Russian states, and despite its name, occurs only rarely in cattle. One common host is the domestic cat, from which human infections are most often acquired. [9] [10] Cowpox virus has also infected a variety of animals in European zoos, such as elephants, resulting in human infection. [11]

Laboratory transmission

Aerosols of concentrated virus may result in Orthopoxvirus infection, especially in unimmunized individuals. [12] In addition, needle sticks with concentrated virus or scratches from infected animals may result in local infection of the skin even in immunized individuals. Cowpox infection in Europe is an occupational hazard for veterinary workers, and to a lesser extent, farm workers. [10]

Signs and symptoms

The initial symptoms of Orthopoxvirus infection include fever, malaise, head and body aches, and occasionally vomiting. With the exception of mpox infection, one lesion is the norm, although satellite lesions may be produced by accidental autoinoculation. Individual lesions, surrounded by inflammatory tissue, develop and progress through macules, papules, vesicles, and pustules, and eventually become dry crusts. (Lesions alone are not diagnostic for Orthopoxvirus infection and may be mistaken for zoonotic Parapoxvirus infections, anthrax or Herpesvirus infections. [10] ) Severe edema and erythema may affect large areas of the body in cases of severe infection. Encephalitis (alteration of mental status and focal neurologic deficits), myelitis (upper- and lower-motor neuron dysfunction, sensory level, and bowel and bladder dysfunction), or both may result from Orthopoxvirus infection. Rarely, orthopoxviruses may be detected in cerebrospinal fluid.[ citation needed ]

Regarding specific Orthopoxvirus infections, human mpox most resembles mild smallpox. [7] Human cowpox is a relatively severe localized infection. A survey of 54 cases reported three cases of generalized infection, including one death. [10]

Treatment

Vaccinia-specific immunoglobulins may be administered to infected individuals. The only product currently available for treatment of complications of Orthopoxvirus infection is vaccinia immunoglobulin (VIG), which is an isotonic sterile solution of the immunoglobulin fraction of plasma from persons vaccinated with vaccinia virus. It is effective for treatment of eczema vaccinatum and certain cases of progressive vaccinia. However, VIG is contraindicated for the treatment of vaccinial keratitis. VIG is recommended for severe generalized vaccinia if the patient is extremely ill or has a serious underlying disease. VIG provides no benefit in the treatment of postvaccinal encephalitis and has no role in the treatment of smallpox. Current supplies of VIG are limited, and its use is reserved for treatment of vaccine complications with serious clinical manifestations. The recommended dosage of the currently available VIG is 0.6 ml/kg of body weight. VIG must be administered intramuscularly and is ideally administered as early as possible after the onset of symptoms. Because therapeutic doses of VIG might be substantial (e.g., 42 ml for a person weighing 70 kg), the product may be administered in divided doses over a 24- to 36-hour period. Doses can be repeated, usually at intervals of 2–3 days, until recovery begins (i.e., no new lesions appear). The CDC is currently the only source of VIG for civilians.[ citation needed ]

Certain antiviral compounds such as tecovirimat (ST-246) [13] have been reported to be 100% active against vaccinia virus or other orthopoxviruses in vitro and among test animals. Tecovirimat has been granted orphan drug status by the Food and Drug Administration (FDA) and is currently under study to determine its safety and effectiveness in humans. Another example is brincidofovir. In June 2021, the FDA approved this drug for the treatment of smallpox in humans, making it the first drug approved for an effectively extinct mechanism of action. The decision followed a priority review by the agency, motivated by growing concern of potential bioweapon development. Since the target virus is eradicated the efficacy could not be directly verified but was inferred via proxy, animal survival following infection by related species of Orthopoxvirus. In contrast, safety data was available from trials of the drug in treating Cytomegalovirus infections in humans. [14]

Imatinib, a compound approved by the FDA for cancer treatment, has been shown to limit the release of extracellular enveloped virions and to protect mice from a lethal challenge with vaccinia. [15] Currently, imatinib and related compounds are being evaluated by the CDC for their efficacy against variola virus and mpox virus.

Lab synthesis

In the summer of 2017, researchers at the University of Alberta recreated horsepox via lab synthesis to conduct research into using viruses to treat cancer. [16]

Related Research Articles

<span class="mw-page-title-main">Cowpox</span> Disease of humans and animals

Cowpox is an infectious disease caused by the cowpox virus (CPXV). It presents with large blisters in the skin, a fever and swollen glands, historically typically following contact with an infected cow, though in the last several decades more often from infected cats. The hands and face are most frequently affected and the spots are generally very painful.

<span class="mw-page-title-main">Smallpox vaccine</span> Vaccine against Variola virus

The smallpox vaccine is the first vaccine to have been developed against a contagious disease. In 1796, British physician Edward Jenner demonstrated that an infection with the relatively mild cowpox virus conferred immunity against the deadly smallpox virus. Cowpox served as a natural vaccine until the modern smallpox vaccine emerged in the 20th century. From 1958 to 1977, the World Health Organization (WHO) conducted a global vaccination campaign that eradicated smallpox, making it the only human disease to be eradicated. Although routine smallpox vaccination is no longer performed on the general public, the vaccine is still being produced to guard against bioterrorism, biological warfare, and mpox.

<span class="mw-page-title-main">Mpox</span> Viral disease of humans and animals

Mpox is an infectious viral disease that can occur in humans and some other animals. Symptoms include a rash that forms blisters and then crusts over, fever, and swollen lymph nodes. The illness is usually mild and most of those infected will recover within a few weeks without treatment. The time from exposure to onset of symptoms ranges from five to twenty-one days and symptoms typically last from two to four weeks. Cases may be severe, especially in children, pregnant women or people with suppressed immune systems.

<span class="mw-page-title-main">Vaccinia</span> Strain of poxvirus

Vaccinia virus is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250 nm, with a mass of approximately 5–10 fg. The vaccinia virus is the source of the modern smallpox vaccine, which the World Health Organization (WHO) used to eradicate smallpox in a global vaccination campaign in 1958–1977. Although smallpox no longer exists in the wild, vaccinia virus is still studied widely by scientists as a tool for gene therapy and genetic engineering.

<i>Poxviridae</i> Family of viruses

Poxviridae is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. There are currently 83 species in this family, divided among 22 genera, which are divided into two subfamilies. Diseases associated with this family include smallpox.

Modified vaccinia Ankara (MVA) is an attenuated (weakened) strain of the vaccinia virus. It is being used as a vaccine against smallpox and mpox, having fewer side effects than smallpox vaccines derived from other poxviruses.

<span class="mw-page-title-main">Camelpox</span> Disease of camels caused by the Camelpox virus

Camelpox is a disease of camels caused by the camelpox virus (CMPV) of the family Poxviridae, subfamily Chordopoxvirinae, and the genus Orthopoxvirus. It causes skin lesions and a generalized infection. Approximately 25% of young camels that become infected will die from the disease, while infection in older camels is generally more mild. Although rare, the infection may spread to the hands of those that work closely with camels.

<span class="mw-page-title-main">Smallpox</span> Eradicated viral disease

Smallpox was an infectious disease caused by variola virus, which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) certified the global eradication of the disease in 1980, making smallpox the only human disease to have been eradicated to date.

<span class="mw-page-title-main">Progressive vaccinia</span> Medical condition

Progressive vaccinia is a rare cutaneous condition caused by the vaccinia virus, characterized by painless but progressive necrosis and ulceration.

<span class="mw-page-title-main">Tecovirimat</span> Antiviral medication

Tecovirimat, sold under the brand name Tpoxx among others, is an antiviral medication with activity against orthopoxviruses such as smallpox and mpox. In 2018 it became the first antipoxviral drug approved in the United States.

Chordopoxvirinae is a subfamily of viruses in the family Poxviridae. Vertebrates and arthropods serve as natural hosts. Currently, 52 species are placed in this subfamily, divided among 18 genera. Diseases associated with this subfamily include smallpox.

<i>Monkeypox virus</i> Species of double-stranded DNA virus

The monkeypox virus, is a species of double-stranded DNA virus that causes mpox disease in humans and other mammals. The monkeypox virus is a zoonotic virus belonging to the orthopoxvirus genus, making it closely related to the variola, cowpox, and vaccinia viruses. MPV is oval-shaped with a lipoprotein outer membrane. The genome is approximately 190 kb.

Vaccinia immune globulin (VIG) is made from the pooled blood of individuals who have been inoculated with the smallpox vaccine. The antibodies these individuals developed in response to the smallpox vaccine are removed and purified. This results in VIG. It can be administered intravenously. It is used to treat individuals who have developed progressive vaccinia after smallpox vaccination.

Orthopoxvirus inclusion bodies are aggregates of stainable protein produced by poxvirus virions in the cell nuclei and/or cytoplasm of epithelial cells in humans. They are important as sites of viral replication.

Raccoonpox virus (RCN) is a double-stranded DNA virus and a member of the orthopoxviruses in the family Poxviridae and subfamily Chordopoxvirinae which consists of eight genera: Avipoxvirus, Capripoxvirus, Leporipoxvirus, Molluscipoxvirus, Orthopoxvirus, Parapoxvirus, Suipoxvirus and Yatapoxvirus Vertebrates are the natural host of Chordopoxvirinae subfamily viruses. More specifically, raccoons are the natural hosts of RCN. RCN was isolated in 1961 from the upper respiratory tissues of 2 raccoons in a group of 92 observably healthy raccoons trapped close to Aberdeen, Maryland.

Rijk Gispen, was a Dutch virologist and former Director of the National Institute of Public Health in the Netherlands. He is well known for his research in immunology and the study of Orthopoxviruses.

Derrick Baxby was a British microbiologist and authority on Orthopoxviruses. He was a senior lecturer in medical microbiology at the University of Liverpool.

The 2022–2023 mpox outbreak in Belgium is part of the larger outbreak of human mpox caused by the West African clade of the monkeypox virus. Belgium was the fifth country, outside of the African countries with endemic mpox, to experience an outbreak in 2022. The first case was documented in Antwerp, Belgium, on 19 May 2022. As of 10 August, Belgium has 546 cases and 1 suspected case.

The 2022–2023 mpox outbreak in Israel is a part of the ongoing outbreak of human mpox caused by the West African clade of the monkeypox virus. The outbreak was first reported in Israel on 20 May 2022 when the Health Ministry announced a suspected case which was confirmed on 21 May 2022. One month later, on 21 June, the first locally transmitted case was reported.

The 2022–2023 mpox outbreak in Singapore is a part of the global outbreak of human mpox caused by the West African clade of the monkeypox virus. According to the Ministry of Health (MOH), Singapore's first imported mpox case was reported on 20 June 2022. It was the first ever confirmed case in Southeast Asia.

References

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  2. 1 2 "Virus Taxonomy: 2020 Release". International Committee on Taxonomy of Viruses (ICTV). March 2021. Retrieved 22 May 2021.
  3. 1 2 Gigante, Crystal M.; Gao, Jinxin; Tang, Shiyuyun; McCollum, Andrea M.; Wilkins, Kimberly; Reynolds, Mary G.; Davidson, Whitni; McLaughlin, Joseph; Olson, Victoria A.; Li, Yu (August 2019). "Genome of Alaskapox Virus, a Novel Orthopoxvirus Isolated from Alaska". Viruses. 11 (8): 708. doi: 10.3390/v11080708 . PMC   6723315 . PMID   31375015.
  4. ↑ Trindade, Giliane S.; Emerson, Ginny L.; Carroll, Darin S.; Kroon, Erna G.; Damon, Inger K. (1 July 2007). "Brazilian Vaccinia Viruses and Their Origins". Emerging Infectious Diseases. 13 (7): 965–972. doi:10.3201/eid1307.061404. ISSN   1080-6040. PMC   2878226 . PMID   18214166.
  5. 1 2 Hendrickson, RC; Wang, C; Hatcher, EL; Lefkowitz, EJ (September 2010). "Orthopoxvirus genome evolution: the role of gene loss". Viruses. 2 (9): 1933–67. doi: 10.3390/v2091933 . PMC   3185746 . PMID   21994715.
  6. ↑ Baxby, Derrick (1988). "Human poxvirus infection after the eradication of smallpox". Epidem, Inf. 100 (3): 321–34. doi:10.1017/s0950268800067078. PMC   2249357 . PMID   2837403.
  7. 1 2 Jezek, Z.; Fenner, F. (1988). Human monkeypox. Basel: Karger. ISBN   3-8055-4818-4.
  8. ↑ Centers for Disease Control Prevention (CDC) (2003). "Update:Multistate Outbreak of Monkeypox - Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003". MMWR. 52 (27): 642–6. PMID   12855947.
  9. ↑ Bennett, M; Gaskell, C.J.; Baxby, D.; Gaskell, R.M.; Kelly, D.F.; Naidoo, J. (1990). "Feline cowpox virus infection". Journal of Small Animal Practice. 31 (4): 167–73. doi: 10.1111/j.1748-5827.1990.tb00760.x .
  10. 1 2 3 4 Baxby, D.; Bennett, M.; Getty, B. (1994). "Human cowpox 1969-93: a review based on 54 cases". Br. J. Dermatol. 131 (5): 598–607. doi:10.1111/j.1365-2133.1994.tb04969.x. PMID   7999588. S2CID   12289212.
  11. ↑ Kurth, A.; Wibbelt G; Gerber H-P; Petschaelis A; Pauli G; Nitsche A. (April 2008). "Rat-to-Elephant-to-Human Transmission of Cowpox Virus". Emerging Infectious Diseases. 14 (4): 670–671. doi:10.3201/eid1404.070817. PMC   2570944 . PMID   18394293.
  12. ↑ Martinez, Mark; Michael P. Bray; John W. Huggins (2000). "A Mouse Model of Aerosol-Transmitted Orthopoxviral Disease". Archives of Pathology & Laboratory Medicine. 124 (3): 362–77. doi:10.5858/2000-124-0362-AMMOAT. PMID   10705388 . Retrieved 11 February 2018.
  13. ↑ Yang G, Pevear DC, Davies MH, et al. (October 2005). "An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus Challenge". J. Virol. 79 (20): 13139–49. doi:10.1128/JVI.79.20.13139-13149.2005. PMC   1235851 . PMID   16189015.
  14. ↑ "FDA approves drug to treat smallpox". FDA. 4 June 2021.
  15. ↑ Reeves, P. M.; Bommarius, B.; Lebeis, S.; McNulty, S.; Christensen, J.; Swimm, A.; Chahroudi, A.; Chavan, R.; Feinberg, M. B.; Veach, D.; Bornmann, W.; Sherman, M.; Kalman, D. (2005). "Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases". Nature Medicine. 11 (7): 731–739. doi:10.1038/nm1265. PMID   15980865. S2CID   28325503.
  16. ↑ Riley, Kim (10 August 2017). "Bioterrorism threats require common global experimentation oversight, expert says". Homeland Preparedness News. Retrieved 7 November 2017.
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