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.

[1] Some orthopoxviruses, including the mpox, cowpox, and buffalopox viruses, have the ability to infect non-reservoir species.

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.

[8] However, human and prairie dog cases have occurred in the US due to contact with animals imported from Ghana,[9] while in May 2022 an outbreak of mpox began spreading globally.

[11] The initial symptoms of Orthopoxvirus infection include fever, malaise, head and body aches, and occasionally vomiting.

Individual lesions, surrounded by inflammatory tissue, develop and progress through macules, papules, vesicles, and pustules, and eventually become dry crusts.

[citation needed] Regarding specific Orthopoxvirus infections, human mpox most resembles mild smallpox.

VIG is recommended for severe generalized vaccinia if the patient is extremely ill or has a serious underlying disease.

Current supplies of VIG are limited, and its use is reserved for treatment of vaccine complications with serious clinical manifestations.

[citation needed] 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.

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.

[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.