Subfamily: Chordopoxvirinae

Genus: Orthopoxvirus


Distinguishing features

The Orthopoxvirus genus includes 13 species, and multiple isolates have been fully sequenced. The species divide into two sister clades; the Eurasian/African orthopoxviruses and the North American orthopoxviruses (Emerson et al., 2009). Extensive serological cross-reactivity and cross-neutralisation exists between the viruses, certainly within the Eurasian/African clade. The host range varies between species and can be broad in laboratory animals and tissue culture, but relatively narrow in nature. For example, members of the species Cowpox virus and Vaccinia virus can infect multiple host species, whereas members of the species Variola virus and Ectromelia virus only infect humans and mice respectively. Most infections are generalized and disseminated and can be fatal. Variola virus, the etiological agent of smallpox, is thought to have been responsible for the deaths of at least 300 million people in the 20th century alone. Viruses in several species are zoonotic, but the zoonotic potential of others is unknown. The natural hosts of most orthopoxviruses are unknown, although, with the exception of variola virus, rodents are commonly implicated. Orthopoxviruses are the most extensively studied poxviruses and our detailed knowledge and understanding of poxvirus biology, morphogenesis, replication and virus host interactions largely come from studies involving these viruses.


Virions are brick-shaped, about 200 × 200 × 250 nm. Infectivity is ether-resistant.

Genome organization and replication

The linear dsDNA genome (approximately 186–228 kbp), putatively encodes between 174–233 proteins; G + C content is about 36%. The central 102 kbp of the genomes, encodes approximately 100 proteins and is extensively conserved amongst members of all species, both in gene content and synteny. The encoded proteins are involved in virus replication, morphogenesis and dissemination. The regions at either end of the genomes encode proteins involved in interacting with the host immune response or provide replicative advantages in the host and, in many cases, are unique to members of the individual orthopoxvirus species. Phylogenetic analyses separate the North American species from the African/Eurasian species and furthermore suggest that there are greater evolutionary distances between each of the North American species than there are between the African/Eurasian species. Extensive analyses of complete genomes of members of the species Cowpox virus suggest a re-examination of this taxon is required to potentially split the current single species into 5–14 species. The unclassified virus Alaskapox virus was isolated in North America but segregates with African/Eurasian orthopoxviruses.

For replication please see discussion under family description.

Species demarcation criteria

Nucleotide sequence identity. Within the conserved, core region of the genome, nucleotide sequence identity of >96% is observed between isolates of all non-North American species. Isolates within a species exhibit >98% nucleotide identity. Where nucleotide identity alone is insufficient to separate species the following further criteria are taken into account:

  • · Amino acid or nucleotide sequence identity between specific, commonly shared genes. Sequence polymorphisms within genes such as the hemagglutinin or A-type inclusion protein can frequently exhibit high levels of variation that provide the resolving power necessary to make demarcation decisions.

  • · Growth characteristics and host range in cell culture. Characteristics of in vitro growth such as the production and morphology of pocks produced on the chorioallantoic membranes of embryonated chicken eggs or plaque characteristics on cell monolayers may distinguish between members of different species.

  • · Disease characteristics. The morbidity, mortality and other distinguishing features of the disease resulting from poxvirus infection can be used to support taxonomic decisions.

  • · Serological criteria, including plaque neutralization tests and cross-protection in animals, may help to identify new, unique isolates and serve as a criterion for taxonomic demarcation.

Related, unclassified viruses

Virus name

Accession number


Alaskapox virus



Virus names and virus abbreviations are not official ICTV designations.