Poxviruses

Abstract Poxviruses are brick‐shaped, enveloped viruses, each containing a linear, double‐stranded DNA ( deoxyribonucleic acid ) genome of 130–380 kilobases (kb). Several family members, including variola , monkeypox , cowpox , vaccinia , orf and molluscum contagiosum viruses , cause disease in humans. Smallpox, which was caused by variola virus , was once responsible for the deaths of millions each year. In 1796, Jenner showed that inoculation of material from a cowpox lesion could protect against smallpox: Vaccination had been introduced into medicine. Moreover, through the use of cowpox and vaccinia virus vaccines, the dread disease of smallpox was eradicated from the natural environment. Although variola virus , the principal poxvirus pathogen, is no longer a public health hazard, the poxviruses have continued to be the focus of intense study because they provide unique systems for investigation of mechanisms important in molecular biology, viral pathogenicity and immunity. Attenuated poxviruses now provide some of the most promising contemporary platforms for broad‐spectrum, live‐virus vaccines. Key concepts Variola virus , which causes smallpox, is one of the most virulent human pathogens. Variola virus is the only virus eradicated from the natural environment. Jenner showed that infection with cowpox could protect against infection with smallpox. Cowpox virus was the original vaccine, hence the name vaccine, from the Latin word vacca for cow. The worldwide eradication of the disease of smallpox was achieved by immunization with vaccines containing live vaccinia viruses (viruses similar to, but more attenuated than, cowpox virus ). Except for variola virus and molluscum contagiosum virus (MCV), most of the poxvirus diseases of humans are zoonoses (diseases transmitted to humans from animals). Among viruses, the poxviruses are unusually independent of host cell functions, employing mainly viral enzymes for viral gene transcription and viral DNA replication in the cytoplasm of infected cells. Poxviruses do not establish latent infections. Poxviruses possess many accessory genes that are not required for virus replication in vitro , but which are advantageous for virus replication in vivo . Most of the accessory proteins encoded by poxviruses of vertebrates interfere with either innate or adaptive immune responses.