''Orthopoxvirus'' is a genus of
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsk ...
es in the family ''
Poxviridae
''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 wit ...
'' and subfamily ''
Chordopoxvirinae
''Chordopoxvirinae'' is a subfamily of viruses in the family ''Poxviridae''. Humans, vertebrates, and arthropods serve as natural hosts. Currently, 52 species are placed in this subfamily, divided among 18 genera. Diseases associated with this s ...
''. Vertebrates, including mammals and humans, and
arthropod
Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and cuticle made of chiti ...
s serve as natural hosts. There are 12 species in this genus. Diseases associated with this genus include
smallpox
Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) c ...
,
cowpox
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 ...
, horsepox,
camelpox
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 ca ...
, and
monkeypox
Monkeypox (also called mpox by the WHO) is an infectious viral disease that can occur in humans and some other animals. Symptoms include fever, swollen lymph nodes, and a rash that forms blisters and then crusts over. The time from exposure t ...
.
The most widely known member of the genus is ''
Variola virus
Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) cer ...
'', 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
''Alaskapox virus'' is a species of the ''Orthopoxvirus'' genus, first documented in 2015 in the United States state of Alaska. As of 2022, there are four known cases of illness caused by the virus, all of which occurred in Fairbanks North Star ...
'', first isolated in 2015.
Microbiology
Structure
![Poxprot](https://upload.wikimedia.org/wikipedia/commons/0/08/Poxprot.jpg)
Orthopoxviruses are enveloped with brick-shaped geometries and virion dimensions around 200 nm wide and 250 nm long.
Genome
Member viruses have linear DNA genomes around 170–250
kb in length.
Lifecycle
Viral replication
Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome an ...
is cytoplasmic. Entry into the host cell is achieved by attachment of the viral proteins to host
glycosaminoglycan
Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case ...
s (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
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ...
and bud as extracellular enveloped virions. In this latter case, the virion is transported to the plasma membrane via microtubules.
Transmission
Natural hosts of orthopoxviruses are
mammals and
arthropod
Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and cuticle made of chiti ...
s. Member viruses are transmitted by respiratory droplets, contact, and zoonosis.
Distribution
Some orthopoxviruses, including the monkeypox, cowpox, and
buffalopox
Buffalopox is caused by ''buffalopox virus'' (BPXV); it is a ''Poxviridae'' for which the natural host is buffalo. It mainly infects buffalo but has been known to infect cows and humans. It is classified in the ''Orthopoxvirus'' (OPV) genus and ...
viruses, have the ability to infect non-reservoir species. Others, such as
ectromelia
Ectromelia is a congenital condition where long bone
The long bones are those that are longer than they are wide. They are one of five types of bones: long, short, flat, irregular and sesamoid. Long bones, especially the femur and tibia, are ...
and
camelpox
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 ca ...
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. 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.
Taxonomy
The genus contains the following species:
* ''
Abatino macacapox virus''
* ''
Akhmeta virus
Akhmeta ( ka, ახმეტა) is a town in Kakheti (Georgia) and is the administrative centre of Akhmeta Municipality. It's situated on the left side of Alazani, close to the Pankisi Gorge. The town is situated at 567m. In 1966, it received th ...
''
* ''
Alaskapox virus
''Alaskapox virus'' is a species of the ''Orthopoxvirus'' genus, first documented in 2015 in the United States state of Alaska. As of 2022, there are four known cases of illness caused by the virus, all of which occurred in Fairbanks North Star ...
''
* ''
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 c ...
''
* ''
Cowpox virus
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 ...
''
* ''
Ectromelia virus
''Ectromelia virus'' (ECTV) is a virus of the family ''Poxviridae'' and the genus ''Orthopoxvirus'' that causes mousepox, a disease of mice. It has only been seen in mouse colonies kept for research purposes but believed that wild populations ...
''
* ''
Monkeypox virus
''Monkeypox virus'' (MPV, MPXV, or hMPXV) is a species of double-stranded DNA virus that causes monkeypox in humans and other mammals. Monkeypox virus is a zoonotic virus belonging to the ''orthopoxvirus'' genus, making it closely related to the ...
''
* ''
Raccoonpox virus
''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, Molluscipox ...
''
* ''
Skunkpox virus''
* ''
Taterapox virus''
* ''
Vaccinia virus
''Vaccinia virus'' (VACV or VV) 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 ...
''
* †''
Variola virus
Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) cer ...
''
* ''
Volepox virus''
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:
Some of the differences in the two trees are attributed to the procedure of passage in producing vaccinia strains. The
Modified vaccinia Ankara
Modified vaccinia Ankara (MVA) is an attenuated (weakened) strain of the vaccinia virus. It is being used as a vaccine (called MVA-BN, brand names: Imvanex in the EU, Imvamune in Canada, and Jynneos in the US) against smallpox and monkeypox, havi ...
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.
[
]
Infection in humans
Zoonoses
Following the eradication of the human-specific variola virus (smallpox), all human ''Orthopoxvirus'' infections are zoonoses
A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human ...
. Monkeypox occurs naturally only in Africa, particularly in the Democratic Republic of the Congo
The Democratic Republic of the Congo (french: République démocratique du Congo (RDC), colloquially "La RDC" ), informally Congo-Kinshasa, DR Congo, the DRC, the DROC, or the Congo, and formerly and also colloquially Zaire, is a country in ...
. However, human and prairie dog cases have occurred in the US due to contact with animals imported from Ghana, while in May of 2022 an outbreak of monkeypox 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. Cowpox virus has also infected a variety of animals in European zoos, such as elephants, resulting in human infection.
Laboratory transmission
Aerosols of concentrated virus may result in'' Orthopoxvirus'' infection, especially in unimmunized individuals. 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.[
]
Signs and symptoms
The initial symptoms of'' Orthopoxvirus ''infection include fever
Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
, malaise, head and body aches, and occasionally vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteri ...
. With the exception of monkeypox infection, one lesion is the norm, although satellite lesions may be produced by accidental autoinoculation. Individual lesions
A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals.
Types
There is no designated classifi ...
, surrounded by inflammatory tissue, develop and progress through macules
A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this s ...
, papules
A papule is a small, well-defined bump in the skin. It may have a rounded, pointed or flat top, and may have a dip. It can appear with a stalk, be thread-like or look warty. It can be soft or firm and its surface may be rough or smooth. Some h ...
, vesicle
Vesicle may refer to:
; In cellular biology or chemistry
* Vesicle (biology and chemistry)
In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form nat ...
s, and pustules
A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this ...
, and eventually become dry crusts. (Lesions alone are not diagnostic for ''Orthopoxvirus ''infection and may be mistaken for zoonotic ''Parapoxvirus
''Parapoxvirus'' is a genus of viruses, in the family ''Poxviridae'', in the subfamily ''Chordopoxvirinae''. Like all members of the family Poxviridae, they are oval, relatively large, double-stranded DNA viruses. Parapoxviruses have a unique s ...
'' infections, anthrax or ''Herpesvirus
''Herpesviridae'' is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ''ἕρπειν ...
'' infections.[) Severe edema and ]erythema
Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not asso ...
may affect large areas of the body in cases of severe infection. Encephalitis (alteration of mental status and focal neurologic deficits), myelitis
Myelitis is inflammation of the spinal cord which can disrupt the normal responses from the brain to the rest of the body, and from the rest of the body to the brain. Inflammation in the spinal cord, can cause the myelin and axon to be damaged re ...
(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
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...
.
Regarding specific ''Orthopoxvirus'' infections, human monkeypox most resembles mild smallpox. Human cowpox is a relatively severe localized infection. A survey of 54 cases reported three cases of generalized infection, including one death.
Treatment
Vaccinia-specific immunoglobulins
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
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
Postvaccinal encephalitis (PVE) is postvaccinal Complication (medicine), complication which was associated with vaccination with vaccinia virus during worldwide smallpox eradication campaign. With mortality ranging between 25 – 30% and lifelong ...
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
Tecovirimat, sold under the brand name Tpoxx among others, is an antiviral medication with activity against orthopoxviruses such as smallpox and monkeypox. It is the first antipoxviral drug approved in the United States. It is an inhibitor of t ...
(ST-246) have been reported to be 100% active against vaccinia virus or other orthopoxviruses ''in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
'' and among test animals. Tecovirimat has been granted orphan drug status by the Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) and is currently under study to determine its safety and effectiveness in humans. Another example is brincidofovir
Brincidofovir, sold under the brand name Tembexa, is an antiviral drug used to treat smallpox. Brincidofovir is a prodrug of cidofovir. Conjugated to a lipid, the compound is designed to release cidofovir intracellularly, allowing for higher int ...
. 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.
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. Currently, imatinib and related compounds are being evaluated by the CDC for their efficacy against variola virus and monkeypox virus.
Lab synthesis
In the summer of 2017, researchers at the University of Alberta
The University of Alberta, also known as U of A or UAlberta, is a Public university, public research university located in Edmonton, Alberta, Canada. It was founded in 1908 by Alexander Cameron Rutherford,"A Gentleman of Strathcona – Alexande ...
recreated horsepox via lab synthesis to conduct research into using viruses to treat cancer.
References
External links
Viralzone: Orthopoxvirus
ICTV
Virus Pathogen Database and Analysis Resource (ViPR): Poxviridae
{{Taxonbar, from=Q740335
Chordopoxvirinae
Virus genera
fr:Orthopoxvirus