Orthopoxvirus

Orthopoxvirus
Virus classification
(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

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

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]

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

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

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

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]

References