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Orthopoxvirus és un gènere de virus dins la família Poxviridae que inclou moltes espècies aïllades en mamífers com el Buffalopox virus, Camelpox virus, Cowpox virus, Monkeypox virus, Rabbitpox virus, Volepox virus i Ectromelia virus. El membre més famós del gènere és Variola virus, que causa smallpox. Un altre orthopoxvirus, Vaccinia virus, fa de vacuna. Els símptomes inicials de la infecció són febre i dolors de cap i musculars entre d’altres. Després hi ha úlceres a la pell i nflamacions dels teixits, encefalitis, etc.
Orthopoxvirus és un gènere de virus dins la família Poxviridae que inclou moltes espècies aïllades en mamífers com el Buffalopox virus, Camelpox virus, Cowpox virus, Monkeypox virus, Rabbitpox virus, Volepox virus i Ectromelia virus. El membre més famós del gènere és Variola virus, que causa smallpox. Un altre orthopoxvirus, Vaccinia virus, fa de vacuna. Els símptomes inicials de la infecció són febre i dolors de cap i musculars entre d’altres. Després hi ha úlceres a la pell i nflamacions dels teixits, encefalitis, etc.
Die Gattung Orthopoxvirus (OPXV) besitzt eine lineare doppelsträngige DNA (130 bis 375Kb) und hat eine Größe von 170 bis 450 nm. Orthopoxvirusinfektionen werden in der Tierseuchengesetzgebung auch als Säugerpocken bezeichnet. Infektionen mit Orthopoxviren zählen in Deutschland zu den meldepflichtigen Tierkrankheiten.[2]
Die Anheftung von Proteinen an der Oberfläche der Virusteilchen (Virionen) an Glykosaminoglykane (GAGs) der Wirtszelle vermittelt deren Endozytose (Makropinozytose) in diese hinein. Die Veirionen können auch durch molekulares Mimikry (englisch apoptotic mimicry) aufgenommen werden. Nach dem Aufreißen der äußeren Virushülle verschmilzt die innere mit der Plasmamembran der Zelle, wodurch das Innere der Virionen mit dem Genom ins Zytoplasma der Wirtszelle freigesetzt wird. Danach werden die ersten („frühen“) Gene im Zytoplasma durch eine virale RNA-Polymerase transkribiert. Diese „frühe“ Expression beginnt ca. 30 Minuten nach der Infektion. Am Ende dieser Phase liegt das Virus-Genom frei im Zytoplasma. In der nächsten („intermediären“) Phase werden weitere Gene exprimiert und lösen die DNA-Replikation des Genoms etwa 100 Minuten nach der Infektion aus. In der letzten („späten“) Phase werden die restlichen („späten“) Gene exprimiert und produzieren alle Strukturproteine. Der Zusammenbau („Assemblierung“) der neuen Virionen beginnt in Virusfabriken des Zytoplasmas, wobei zunächst noch unreife, kugelige Partikel entstehen. Diese Viruspartikel reifen dann in der Wirtszellen zu ziegelsteinförmigen reifen Virion (en. intracellular mature virion, IMV). Die IMVs können bei einer Zelllyse freigesetzt werden oder eine zweite Doppelmembran aus dem Golgi-Apparat erwerben und dann als externe umhüllte Virionen (en. external enveloped virion, EEV) austreten (Exozytose).[3]
Die Gattung Orthopoxvirus umfasst folgende Arten mit deren Varietäten:
Die Gattung Orthopoxvirus (OPXV) besitzt eine lineare doppelsträngige DNA (130 bis 375Kb) und hat eine Größe von 170 bis 450 nm. Orthopoxvirusinfektionen werden in der Tierseuchengesetzgebung auch als Säugerpocken bezeichnet. Infektionen mit Orthopoxviren zählen in Deutschland zu den meldepflichtigen Tierkrankheiten.
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]
Orthopoxviruses are enveloped with brick-shaped geometries and virion dimensions around 200 nm wide and 250 nm long.[1]
Member viruses have linear DNA genomes around 170–250 kb in length.[1]
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]
Natural hosts of orthopoxviruses are mammals and arthropods. Member viruses are transmitted by respiratory droplets, contact, and zoonosis.[1]
Some orthopoxviruses, including the mpox (formerly known as monkeypox), 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.
The genus contains the following species:[2][5]
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:[6]
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.[6]
Following the eradication of the human-specific variola virus (smallpox), all human Orthopoxvirus infections are zoonoses.[7] Monkeypox occurs naturally only in Africa, particularly in the Democratic Republic of the Congo.[8] However, human and prairie dog cases have occurred in the US due to contact with animals imported from Ghana,[9] while in May of 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.[10][11] Cowpox virus has also infected a variety of animals in European zoos, such as elephants, resulting in human infection.[12]
Aerosols of concentrated virus may result in Orthopoxvirus infection, especially in unimmunized individuals.[13] 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.[11]
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.[11]) 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.
Regarding specific Orthopoxvirus infections, human mpox most resembles mild smallpox.[8] Human cowpox is a relatively severe localized infection. A survey of 54 cases reported three cases of generalized infection, including one death.[11]
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.
Certain antiviral compounds such as tecovirimat (ST-246)[14] 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.[15]
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.[16] Currently, imatinib and related compounds are being evaluated by the CDC for their efficacy against variola virus and mpox virus.
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.[17]
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. 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.
Orthopoxvirus es un género vírico de poxvirus incluyendo muchas especies aisladas de mamíferos no humanos, como Buffalopox virus, Camelpox virus, Cowpox virus, Monkeypox virus, Rabbitpox virus, Sealpox virus, Volepox virus y Ectromelia virus, que causa viruela del ratón. El más famoso miembro del género es Variola virus, que causa viruela. Fue destruido usando otro orthopoxvirus, el Vaccinia virus.
Los miembros del género Orthopoxvirus lo son también de la subfamilia Chordopoxvirinae, que es una división de dsADN de la familia viral Poxviridae. Algunos síntomas de esta son olores desagradables, dolores de cabeza, visión doble, máreos y ceguera.
Los virus Orthopox se distribuyen universalmente. Todos los Orthopoxvirus de mamíferos no humanos pueden considerarse capaces de establecer infecciones en humanos. Las zoonosis de muchas de esas enfermedades aisladas han sido reportadas.
Los aerosoles de concentrados de virus pueden resultar en infección por Orthopox, especialmente en individuos no inmunizados. Pinchazos de agujas hipodérmicas, especialmente con carga de virus, pueden resultar en severa infección local de la piel, aún en individuos inmunizados.
Se transmiten primariamente por microgotas respiratorias, por contacto directo con fluidos corporales u objetos contaminados con dichos fluidos, pueden también transmitir la infección.
Los síntomas iniciales de una infección por Orthopoxvirus incluye fiebre, malestares, dolores de cuerpo y de cabeza, y a veces acompañados de vómitos.
Los síntomas iniciales incluyen fiebre, malestares, dolores de cuerpo y de cabeza, y a veces acompañados de vómitos. Las lesiones, las cuales desarrollan en cráteres úlceras rodeadas de tejido inflamado y eventualmente cubiertas de costras oscuras gruesas, son los característicos indicadores de infección por Orthopox. En caso de grave infección, hay severo edema y eritema que afecta grandes áreas. La encefalitis (alteración del estatus mental y déficits focales neurológicos), mielitis (disfunciones motoras neuronales, disfunciones del nivel sensorio de intestinos y de vejiga), o ambos pueden resultar de una infección por Orthopoxvirus. Raramente, los Orthopoxvirus pueden detectarse en fluido cerebroespinal. Algunas infecciones de mamíferos por Orthopoxvirus se conocen por resultar en alta tasa de morbi-mortalidad.
Las vacunas específicas de inmunoglobulinas pueden administrarse a individuos infectados. A veces, el único fármaco corrientemente disponible para tratar las complicaciones de una infección por Orthopox es la Vacuna de Inmunoglobulina (VIG), que es una solución isotónica estéril de una fracción de inmunoglobulina en plasma sanguíneo de personas vacunadas con la vacuna vaccinia. Es efectiva para tratamiento del eczema vacunal y ciertos casos de vaccinia progresiva. Sin embargo, VIG está contraindicada para tratar queratitis vacunal. VIG se recomienda para vaccinia severa y generalizada, si el paciente está extremadamente enfermo y/o tiene severos altibajos. VIG no da beneficios en el tratamiento de encefalitis postvacuna, y no tiene una función en tratar la viruela. El suministro común de VIG es limitado, y su uso debería reservarse para tratar complicaciones vacunales que a veces traen manifestaciones clínicas serias. La dosis recomendada de VIG en tratar tales complicaciones es de 0,6 ml/kg de masa corporal. El VIG debe administrarse por vía intramuscular y tan pronto y temprano como se adviertan los síntomas. Debido a que la dosis terapéutica de VIG puede ser sustancial (e.g., 42 ml para una persona de 70 kg), el producto puede administrarse en dosis divididas en un periodo de 24- a 36 h. La dosis puede repetirse, usualmente en intervalos de 2--3 días, hasta que ocurra reversión (e.g., que no aparezcan nuevas lesiones). Las futuras reformulaciones de VIG pueden requerir inyección intravenosa, con una cuidadosa observación de las indicaciones del prospecto medicinal en el envase, para una correcta dosis y ruta de administración. CDC es corrientemente la única fuente de VIG para la población civil (ver Disponibilidad de Vacuna Vaccinia para información de contacto). La Administración Estadounidense de Drogas y Alimentos no ha aprobado ningún uso de compuestos antivirales para tratar las infecciones de virus vaccinia o de otras infecciones por Orthopoxvirus, incluyendo la viruela. Ciertos compuestos antivirales (Siga-246) han sido reportados como 100% activos contra el virus vaccinia u otros Orthopoxvirus in vitro y en test de animales. ST-246 no tiene estatus de droga por la FDA, y sigue bajo estudios para determinar su seguridad y efectividad en humanos; y quedan pendientes también cuestiones sobre dosis inocuas efectivas, posología y longitud de la administración de estos compuestos antivirales. Aún hay insuficiente información como para recomendar cualquier compuesto antiviral para tratar complicaciones postvacunación o infecciones por Orthopoxvirus, incluyendo la viruela.
Datos: Q740335
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Especies: Orthopoxvirus
Orthopoxvirus es un género vírico de poxvirus incluyendo muchas especies aisladas de mamíferos no humanos, como Buffalopox virus, Camelpox virus, Cowpox virus, Monkeypox virus, Rabbitpox virus, Sealpox virus, Volepox virus y Ectromelia virus, que causa viruela del ratón. El más famoso miembro del género es Variola virus, que causa viruela. Fue destruido usando otro orthopoxvirus, el Vaccinia virus.
Orthopoxvirus è un genere di virus a DNA a doppio filamento rivestiti da una doppia membrana virale, appartenenti alla famiglia Poxviridae, sottofamiglia Chordopoxvirinae (Poxviridae che infettano i vertebrati).
Gli Orthopoxvirus (OPV) sono virus dei vertebrati di grandi dimensioni, morfologicamente identici, correlati antigenicamente fra di loro, che si replicano nel citoplasma delle cellule ospiti. Questi virus possiedono un genoma a DNA a doppia elica lineare di circa 200 KBP contenente ripetizioni terminali invertite di diverse dimensioni, con un contenuto di Guanina-Citosina di circa il 35%[2].
Gli Orthopoxvirus misurano 250 per 200 nanometri e possiedono una doppia membrana virale: una membrana esterna, di struttura tubolare e presente quando il virus è al di fuori della cellula (proviene dalla membrana della cellula infettata), e una membrana interna, propria del virus. Al microscopio elettronico, il capside ha la forma di un manubrio, ai cui lati sono presenti degli ammassi di proteine, detti "corpi laterali", di cui si ignora la funzione. All'interno del capside c'è il suo DNA, composto da circa 185 000 paia di basi e una decina circa di enzimi coinvolti nella trascrizione del DNA.
I virus del genere Orthopoxvirus si legano a recettori sulla membrana plasmatica delle cellule ospiti e quindi vi penetrano attraverso vacuoli fagocitari della cellula. Il genoma virale viene replicato nel citoplasma, dove vengono quindi assemblate le particelle virali. Le nuove particelle virali compaiono all'interno della cellula dopo 4-5 ore dall'infezione: hanno forma rotonda o ovale e dimensioni più grandi delle particelle virali mature. Dopo circa 2 ore compaiono le particelle virali mature; la moltiplicazione virale continua per altre 16-24 ore finché la cellula ospite viene lisata, rilasciando il virus infettante che può entrare nelle cellule circostanti[3]
Le relazioni antigeniche tra gli Orthopoxvirus si determinano per mezzo di estratti di cellule infette. Possono essere messi in evidenza fino a 20 antigeni in grado di fornire linee di precipitazione con sieri antivirali. Gli Orthopoxvirus sono molto simili antigenicamente e con la reazione di precipitazione evidenzia che differiscono l'uno dall'altro in genere per non più di un antigene. Nel nucleo di tutti i Poxviridae c'è un antigene in comune (antigene Nucleo-Proteico, NP)[4][5]. Oltre a questi antigeni strutturali, vengono prodotti emoagglutinine e antigeni solubili.
La tassonomia degli Orthopoxvirus è basata su caratteristiche biologiche, per esempio la suscettibilità degli animali ospiti, la temperatura di crescita in coltura cellulare o sulla membrana corionallantoidea dell'embrione di pollo, sulla morfologia delle lesioni virali prodotta sulla membrana corionallantoidea embrionaria, e sulle mappe di restrizione del DNA genomico[2]. Di recente sono stati sviluppati metodi basati sulla Real time PCR e il sequenziamento del DNA [6]
Sono noti 12 specie di Orthopoxvirus,[1] quattro dei quali (il virus del vaiolo umano, delle scimmie, il bovino e il Vaccinia) possono infettare gli esseri umani[7]:
Orthopoxvirus è un genere di virus a DNA a doppio filamento rivestiti da una doppia membrana virale, appartenenti alla famiglia Poxviridae, sottofamiglia Chordopoxvirinae (Poxviridae che infettano i vertebrati).
O Orthopoxvirus é um dos maiores vírus que infectam seres humanos, com cerca de 300 nanômetros de diâmetro (nm), o que é suficientemente grande para ser visto como um ponto ao microscópio óptico (o único vírus que causa doença também visível desta forma é o vírus do molusco contagioso). O mais famoso membro deste gênero é o Varíola virus, que causa a varíola.
Alguns Orthopoxvirus tem a capacidade de infectar espécies não hospedeiras, tais como o vírus da varíola dos macacos que é capaz de estabelecer a infecção em seres humanos.[1]
Os vestígios do vírus variólico foram encontrados em 2016, em uma múmia infantil enterrada em uma cripta de uma igreja na Lituânia, que data de cerca de 1654[2]
Aerossóis de vírus concentrado podem resultar em infecção Orthopox, especialmente em indivíduos não imunizados.[3]
|coautor= (ajuda); Verifique data em: |acessodata= (ajuda); |acessodata= requer |url= (ajuda) |coautor= (ajuda) O Orthopoxvirus é um dos maiores vírus que infectam seres humanos, com cerca de 300 nanômetros de diâmetro (nm), o que é suficientemente grande para ser visto como um ponto ao microscópio óptico (o único vírus que causa doença também visível desta forma é o vírus do molusco contagioso). O mais famoso membro deste gênero é o Varíola virus, que causa a varíola.
