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.
Microbiology
Structure
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 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.
Transmission
Natural hosts of orthopoxviruses are mammals and arthropods. Member viruses are transmitted by respiratory droplets, contact, and zoonosis.
Distribution
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. 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
Alaskapox virus
Camelpox virus
Cowpox virus
Ectromelia virus
Monkeypox virus
Raccoonpox virus
Skunkpox virus
Taterapox virus
Vaccinia virus
†Variola virus
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 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. Monkeypox occurs naturally only in Africa, particularly in the Democratic Republic of the Congo. 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 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. Cowpox virus has also infected a variety of animals in European zoos, such as elephants, resulting in human infection.