{{short description|Genus of viruses (poxes)}} {{Use dmy dates|date=April 2017}} {{Virusbox | image = | image_alt = | image_caption = | taxon = Orthopoxvirus | synonyms = | synonyms_ref = | subdivision_ranks = Species | subdivision = See text }}
'''''Orthopoxvirus''''' is a genus of viruses in the family ''Poxviridae'' and subfamily ''Chordopoxvirinae''. Vertebrates, including mammals and reptiles, and arthropods serve as natural hosts. There are 12 known species in this genus. Diseases associated with this genus include smallpox, cowpox, horsepox, camelpox, and mpox.<ref name=ViralZone>{{cite web|title=Viral Zone|url=http://viralzone.expasy.org/all_by_species/149.html|publisher=ExPASy|access-date=15 June 2015|archive-date=18 June 2015|archive-url=https://web.archive.org/web/20150618214924/http://viralzone.expasy.org/all_by_species/149.html|url-status=live}}</ref><ref name=ICTV>{{cite web |title=Virus Taxonomy: 2020 Release |url=https://ictv.global/taxonomy |publisher=International Committee on Taxonomy of Viruses (ICTV) |date=March 2021 |access-date=22 May 2021 |archive-date=8 April 2020 |archive-url=https://web.archive.org/web/20200408062550/https://ictv.global/taxonomy |url-status=live }}</ref> 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 Borealpox virus, first isolated in 2015.<ref name="ReferenceA">{{Cite journal|last1=Gigante|first1=Crystal M.|last2=Gao|first2=Jinxin|last3=Tang|first3=Shiyuyun|last4=McCollum|first4=Andrea M.|last5=Wilkins|first5=Kimberly|last6=Reynolds|first6=Mary G.|last7=Davidson|first7=Whitni|last8=McLaughlin|first8=Joseph|last9=Olson|first9=Victoria A.|last10=Li|first10=Yu|date=August 2019|title=Genome of Alaskapox Virus, a Novel Orthopoxvirus Isolated from Alaska|journal=Viruses|language=en|volume=11|issue=8|pages=708|doi=10.3390/v11080708|pmc=6723315|pmid=31375015|doi-access=free}}</ref>
== Microbiology == ===Structure=== [[File:Poxprot.jpg|thumb|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.<ref name="ViralZone" />
=== Genome === Member viruses have linear double-stranded DNA genomes around 170–250 kb in length.<ref name="ViralZone" />
===Lifecycle=== thumb|''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.<ref name=ViralZone />
=== Transmission === Natural hosts of orthopoxviruses are mammals and arthropods. Member viruses are transmitted by respiratory droplets, contact, and zoonosis.<ref name="ViralZone" />
==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.<ref>{{Cite journal|title = Brazilian Vaccinia Viruses and Their Origins|journal = Emerging Infectious Diseases|date = 2007-07-01|issn = 1080-6040|pmc = 2878226|pmid = 18214166|pages = 965–972|volume = 13|issue = 7|doi = 10.3201/eid1307.061404|first1 = Giliane S.|last1 = Trindade|first2 = Ginny L.|last2 = Emerson|first3 = Darin S.|last3 = Carroll|first4 = Erna G.|last4 = Kroon|first5 = Inger K.|last5 = Damon}}</ref> 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|date=November 2022}}
==Taxonomy==
The genus contains the following species, listed by scientific name and followed by the exemplar virus of the species:<ref>{{cite web|title=Virus Taxonomy: 2024 Release|url=https://ictv.global/taxonomy|publisher=International Committee on Taxonomy of Viruses|access-date=23 March 2025}}</ref><ref>{{cite web|title=Species List: ''Poxviridae''|url=https://ictv.global/report/chapter/poxviridae/taxonomy/poxviridae|publisher=International Committee on Taxonomy of Viruses|access-date=23 March 2025}}</ref>
* ''Orthopoxvirus abatinomacacapox'', Orthopoxvirus Abatino * ''Orthopoxvirus akhmetapox'', Akhmeta virus * ''Orthopoxvirus camelpox'', Camelpox virus * ''Orthopoxvirus cowpox'', Cowpox virus * ''Orthopoxvirus ectromelia'', Ectromelia virus * ''Orthopoxvirus monkeypox'', Monkeypox virus * ''Orthopoxvirus raccoonpox'', Raccoonpox virus * ''Orthopoxvirus skunkpox'', Skunkpox virus * ''Orthopoxvirus taterapox'', Taterapox virus * ''Orthopoxvirus vaccinia'', Vaccinia virus * ''Orthopoxvirus variola'', Variola virus * ''Orthopoxvirus volepox'', Volepox virus
The related Borealpox virus, also known as Alaskapox virus, has not been classified as of 2024.<ref name="ReferenceA" /><ref name=":0">{{Cite web |title=Genus: Orthopoxvirus {{!}} ICTV |url=https://ictv.global/report/chapter/poxviridae/poxviridae/orthopoxvirus |access-date=2024-08-23 |website=ictv.global |archive-date=18 August 2024 |archive-url=https://web.archive.org/web/20240818225057/https://ictv.global/report/chapter/poxviridae/poxviridae/orthopoxvirus |url-status=live }}</ref>
=== 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:<ref name=pmid21994715>{{cite journal |last1=Hendrickson |first1=RC |last2=Wang |first2=C |last3=Hatcher |first3=EL |last4=Lefkowitz |first4=EJ |title=Orthopoxvirus genome evolution: the role of gene loss. |journal=Viruses |date=September 2010 |volume=2 |issue=9 |pages=1933–67 |doi=10.3390/v2091933 |pmid=21994715 |pmc=3185746|doi-access=free }}</ref>
{|class=wikitable |+''Orthopoxvirus'' phylogeny ! By sequence !! By gene content |- | {{clade sequential |Orthopoxvirus ectromelia |Orthopoxvirus cowpox, Germany and Brighton |Orthopoxvirus taterapox, Orthopoxvirus camelpox, Orthopoxvirus variola |Orthopoxvirus monkeypox |Orthopoxvirus cowpox, GRI strain |Orthopoxvirus vaccinia, including rabbitpox and horsepox }} | {{clade sequential |Orthopoxvirus ectromelia |Orthopoxvirus cowpox |Horsepox |Orthopoxvirus vaccinia, including rabbitpox |Orthopoxvirus variola |Orthopoxvirus taterapox, Orthopoxvirus camelpox, Orthopoxvirus monkeypox }} |}
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.<ref name=pmid21994715/>
==Infection in humans== ===Zoonoses=== Following the eradication of the human-specific variola virus (smallpox), all human ''Orthopoxvirus'' infections are zoonoses.<ref name=baxby1988>{{cite journal|last=Baxby|first=Derrick|author-link = Derrick Baxby|title=Human poxvirus infection after the eradication of smallpox|journal=Epidem, Inf.|date=1988|volume=100|issue=3|pages=321–34|doi=10.1017/s0950268800067078|pmid=2837403|pmc=2249357}}</ref> Mpox occurs naturally only in Africa, particularly in the Democratic Republic of the Congo.<ref name=jezek1988>{{cite book|title=Human monkeypox|date=1988|publisher=Karger|location=Basel|isbn=3-8055-4818-4|author=Jezek, Z.|author2=Fenner, F.}}</ref> However, human and prairie dog cases have occurred in the US due to contact with animals imported from Ghana,<ref name=mmwr>{{cite journal|title=Update:Multistate Outbreak of Monkeypox - Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003|journal=MMWR|date=2003|volume=52|issue=27|pages=642–6|pmid=12855947|author1=Centers for Disease Control Prevention (CDC)}}</ref> 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.<ref>{{cite journal|last=Bennett|first=M|author2=Gaskell, C.J. |author3=Baxby, D. |author4=Gaskell, R.M. |author5=Kelly, D.F. |author6=Naidoo, J. |title=Feline cowpox virus infection|journal=Journal of Small Animal Practice|date=1990|volume=31|issue=4|pages=167–73 |doi=10.1111/j.1748-5827.1990.tb00760.x|doi-access=free}}</ref><ref name=baxby1994>{{cite journal|last=Baxby|first=D.|author2=Bennett, M. |author3=Getty, B. |title=Human cowpox 1969-93: a review based on 54 cases|journal=Br. J. Dermatol.|date=1994|volume=131|issue=5|pages=598–607|pmid=7999588|doi=10.1111/j.1365-2133.1994.tb04969.x|s2cid=12289212}}</ref> Cowpox virus has also infected a variety of animals in European zoos, such as elephants, resulting in human infection.<ref>{{cite journal|last=Kurth|first=A.|author2=Wibbelt G |author3=Gerber H-P |author4=Petschaelis A |author5=Pauli G |author6=Nitsche A.|title=Rat-to-Elephant-to-Human Transmission of Cowpox Virus|journal= Emerging Infectious Diseases|date=April 2008|volume=14|issue=4|pages=670–671|pmc=2570944|pmid=18394293|doi=10.3201/eid1404.070817}}</ref>
===Laboratory transmission=== Aerosols of concentrated virus may result in ''Orthopoxvirus'' infection, especially in unimmunized individuals.<ref>{{cite journal|last=Martinez|first=Mark|author2=Michael P. Bray|author3=John W. Huggins|title=A Mouse Model of Aerosol-Transmitted Orthopoxviral Disease|journal=Archives of Pathology & Laboratory Medicine|volume=124|issue=3|pages=362–77|url=http://www.archivesofpathology.org/doi/pdf/10.1043/0003-9985%282000%29124%3C0362:AMMOAT%3E2.0.CO%3B2|access-date=11 February 2018|year=2000|pmid=10705388|doi=10.5858/2000-124-0362-AMMOAT|archive-date=23 August 2023|archive-url=https://web.archive.org/web/20230823115423/https://meridian.allenpress.com/aplm|url-status=live|url-access=subscription}}</ref> 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.<ref name=baxby1994/>
===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.<ref name=baxby1994/>) With severe infections, severe edema and erythema may affect large areas of the body. 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|date=November 2022}}
Regarding specific ''Orthopoxvirus'' infections, human mpox most resembles mild smallpox.<ref name="jezek1988" /> Human cowpox is a relatively severe localized infection. A survey of 54 cases reported three cases of generalized infection, including one death.<ref name="baxby1994" />
===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|date=November 2022}}
Certain antiviral compounds such as tecovirimat (ST-246)<ref>{{cite journal |vauthors=Yang G, Pevear DC, Davies MH, etal |title=An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus Challenge |journal=J. Virol. |volume=79 |issue=20 |pages=13139–49 |date=October 2005 |pmid=16189015 |pmc=1235851 |doi=10.1128/JVI.79.20.13139-13149.2005 }}</ref> 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.<ref>{{Cite journal|url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-drug-treat-smallpox|title=FDA approves drug to treat smallpox|journal=FDA|date=4 June 2021|access-date=11 June 2021|archive-date=8 June 2021|archive-url=https://web.archive.org/web/20210608011633/https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-drug-treat-smallpox|url-status=dead}}</ref>
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.<ref>{{Cite journal | last1 = Reeves | first1 = P. M. | last2 = Bommarius | first2 = B. | last3 = Lebeis | first3 = S. | last4 = McNulty | first4 = S. | last5 = Christensen | first5 = J. | last6 = Swimm | first6 = A. | last7 = Chahroudi | first7 = A. | last8 = Chavan | first8 = R. | last9 = Feinberg | first9 = M. B. | doi = 10.1038/nm1265 | last10 = Veach | first10 = D. | last11 = Bornmann | first11 = W. | last12 = Sherman | first12 = M. | last13 = Kalman | first13 = D. | s2cid = 28325503 | title = Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases | journal = Nature Medicine | volume = 11 | issue = 7 | pages = 731–739 | year = 2005 | pmid = 15980865}}</ref> 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.<ref>{{Cite news|url=https://homelandprepnews.com/featured/23673-bioterrorism-threats-require-common-global-experimentation-oversight-expert-says/|title=Bioterrorism threats require common global experimentation oversight, expert says|last=Riley|first=Kim|date=2017-08-10|work=Homeland Preparedness News|access-date=2017-11-07|language=en-US|archive-date=27 May 2023|archive-url=https://web.archive.org/web/20230527151908/https://homelandprepnews.com/featured/23673-bioterrorism-threats-require-common-global-experimentation-oversight-expert-says/|url-status=live}}</ref>
==References== {{Reflist}}
==External links== * [http://viralzone.expasy.org/all_by_species/149.html '''Viralzone''': Orthopoxvirus] * [http://ictvonline.org/virusTaxonomy.asp '''ICTV'''] * [https://www.viprbrc.org/brc/home.spg?decorator=pox Virus Pathogen Database and Analysis Resource (ViPR): Poxviridae]
{{Viral cutaneous conditions}} {{Baltimore classification}}
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Category:Chordopoxvirinae Category:Virus genera