Poxviruses are a family of large DNA viruses that replicate entirely within the cytoplasm of infected cells, unlike most other DNA viruses which use the host cell’s nucleus. Historically, this family is significant due to smallpox, a devastating disease caused by the variola virus, globally eradicated in 1980 through vaccination. The name “pox” originates from a Middle English word meaning pustule or eruptive sore, reflecting the characteristic skin lesions these viruses often cause. Poxviruses remain relevant in public health today.
Characteristics of Pox Viruses
Poxviruses are large, complex viruses, typically brick-shaped or ovoid, measuring 220 to 450 nanometers. They contain a double-stranded DNA genome (130-375 kilobase pairs) and various enzymes and proteins for replication. Unlike most DNA viruses, poxviruses replicate entirely within the cytoplasm, forming distinct “factories” where DNA synthesis and virion assembly occur.
Poxviruses encode many of their own enzymes for DNA replication and gene expression, such as DNA-dependent RNA polymerase and DNA polymerase. This self-sufficiency allows them to largely bypass the host cell’s nuclear machinery. Early viral genes are transcribed by viral RNA polymerase in the cytoplasm, leading to proteins that facilitate DNA replication.
Diseases Caused by Pox Viruses
Poxviruses cause a range of human diseases, with varying levels of severity and impact. Smallpox, caused by the variola virus, was historically one of the most feared infectious diseases, responsible for an estimated 300 million deaths in the 20th century alone. The disease manifested with initial symptoms like fever and vomiting, followed by characteristic fluid-filled blisters with a dimpled center that would scab over, leaving scars. Variola major, the more common form, had a mortality rate of about 30%, while variola minor was milder with a 0.1–2% fatality rate.
Monkeypox, now often referred to as mpox, is another orthopoxvirus infection that has gained prominence, particularly with recent global outbreaks. It causes a disease that clinically resembles smallpox, presenting with a rash, fever, and swollen lymph nodes. While less severe than smallpox, mpox can still be serious, especially in children, pregnant individuals, or those with weakened immune systems. The 2022 global mpox outbreak, for example, involved over 90,000 cases worldwide, with a mortality rate of approximately 0.03% in reported cases outside of Africa.
Beyond smallpox and mpox, other human poxvirus infections exist, though they are generally less common or cause localized disease. Molluscum contagiosum virus, an obligate human pathogen, causes distinctive pearly, flesh-colored, umbilicated skin lesions, typically 2–5 mm in diameter, which can persist for months or years. Cowpox, a zoonotic infection, usually results in localized ulcerating lesions on the hands or other sites where the virus enters through skin abrasions. These infections underscore the diverse clinical presentations within the poxvirus family.
Transmission and Management
Poxviruses can transmit through various routes, depending on the specific virus. Direct contact with lesions, respiratory droplets, and contaminated materials (fomites) are common modes of spread. Zoonotic transmission, where the virus moves from animals to humans, is also a significant pathway for many poxviruses, including mpox and cowpox. Mpox can spread through close contact with infected animals, or from person-to-person through direct contact with infected skin or body fluids, including during sexual activity.
Management strategies for poxvirus infections focus on prevention through vaccination and treatment with antiviral medications when available. The smallpox vaccine, which utilized the vaccinia virus, was instrumental in eradicating smallpox and also offers protection against other orthopoxviruses like mpox. For mpox, the JYNNEOS vaccine is approved and provides protection with fewer side effects than older vaccinia-based vaccines.
Antiviral treatments are available for severe cases of poxvirus infections. Tecovirimat (TPOXX) is an antiviral medication approved for the treatment of smallpox and mpox, although its effectiveness against smallpox in humans has not been definitively proven due to the disease’s eradication. It works by blocking viral egress from infected cells. Other antivirals like cidofovir and brincidofovir are also stockpiled and can be used for severe cases, though their use is generally under investigational protocols. Supportive care, including pain management and addressing secondary infections, is also a component of treatment, particularly for less severe cases.
Pox Viruses Today
In the era following smallpox eradication, poxviruses continue to be a focus of public health attention. Ongoing surveillance efforts are in place to monitor for the emergence of new poxvirus infections and potential outbreaks. The 2022 global mpox outbreak highlighted the continued relevance of these viruses, demonstrating their capacity for widespread transmission, even in non-endemic regions. This outbreak, predominantly affecting men who have sex with men, underscored the importance of adapting public health responses to evolving transmission patterns.
Poxviruses also remain a consideration in biodefense strategies, given the historical impact of smallpox and the potential for its deliberate reintroduction. While smallpox no longer circulates naturally, maintaining preparedness against such threats is a priority. The development and stockpiling of vaccines and antiviral treatments, such as tecovirimat, are part of this ongoing readiness. The continued study of poxviruses helps in understanding their biology and developing improved countermeasures against both known and potentially emerging strains.