cowpox cowpox cowpox is an infectious disease caused by the cowpox virus (cpxv). it presents with large blisters in the skin, a fever and swollen glands, historically typically following contact with an infected cow, though in the last several decades more often (though overall rarely) from infected cats. the hands and face are most frequently affected and the spots are generally very painful. cowpox virus electron micrograph of three cowpox virus particles virus classification (unranked): virus realm: varidnaviria kingdom: bamfordvirae phylum: nucleocytoviricota class: pokkesviricetes order: chitovirales family: poxviridae genus: orthopoxvirus species: cowpox virus cowpoxcowpox lesions on patient's forearm on day 7 after onset of illness. the hemagglutinin gene of the isolate clustered with a russian cowpox virus strain, and the more distantly, with other cowpox and vaccinia virus strains. the patient's dog had orthopoxvirus-specific antibodies, indicating a possible transmission route.specialtyinfectious diseases, veterinary medicine the virus, part of the genus orthopoxvirus, is closely related to the vaccinia virus. the virus is zoonotic, meaning that it is transferable between species, such as from cat to human. the transferral of the disease was first observed in dairy workers who touched the udders of infected cows and consequently developed the signature pustules on their hands. cowpox is more commonly found in animals other than bovines, such as rodents. cowpox is similar to, but much milder than, the highly contagious and often deadly smallpox disease. its close resemblance to the mild form of smallpox and the observation that dairy farmers were immune to smallpox inspired the modern smallpox vaccine, created and administered by english physician edward jenner. the first description of cowpox was given by jenner in 1798. "vaccination" is derived from the latin adjective vaccinus, meaning "of or from the cow". once vaccinated, a patient develops antibodies that make them immune to cowpox, but they also develop immunity to the smallpox virus, or variola virus. the cowpox vaccinations and later incarnations proved so successful that in 1980, the world health organization announced that smallpox was the first disease to be eradicated by vaccination efforts worldwide. other orthopox viruses remain prevalent in certain communities and continue to infect humans, such as the cowpox virus in europe, vaccinia in brazil, and monkeypox virus in central and west africa. medical use naturally occurring cases of cowpox were not common, but it was discovered that the vaccine could be "carried" in humans and reproduced and disseminated human-to-human. jenner's original vaccination used lymph from the cowpox pustule on a milkmaid, and subsequent "arm-to-arm" vaccinations applied the same principle. as this transfer of human fluids came with its own set of complications, a safer manner of producing the vaccine was first introduced in italy. the new method used cows to manufacture the vaccine using a process called "retrovaccination", in which a heifer was inoculated with humanized cowpox virus, and it was passed from calf to calf to produce massive quantities efficiently and safely. this then led to the next incarnation, "true animal vaccine", which used the same process but began with naturally-occurring cowpox virus, and not the humanized form. this method of production proved to be lucrative and was taken advantage of by many entrepreneurs needing only calves and seed lymph from an infected cow to manufacture crude versions of the vaccine. w. f. elgin of the national vaccine establishment presented his slightly refined technique to the conference of state and provincial boards of health of north america. a tuberculosis-free calf, stomach shaved, would be bound to an operating table, where incisions would be made on its lower body. glycerinated lymph from a previously inoculated calf was spread along the cuts. after a few days, the cuts would have scabbed or crusted over. the crust was softened with sterilized water and mixed with glycerin, which disinfected it, then stored hermetically sealed in capillary tubes for later use. at some point, the virus in use was no longer cowpox, but vaccinia. scientists have not determined exactly when the change or mutation occurred, but the effects of vaccinia and cowpox virus as vaccine are nearly the same. the virus is found in europe, and mainly in the uk. human cases today are very rare and most often contracted from domestic cats. the virus is not commonly found in cattle; the reservoir hosts for the virus are woodland rodents, particularly voles. from these rodents, domestic cats contract and transmit the virus to humans. symptoms in cats include lesions on the face, neck, forelimbs, and paws, and less commonly upper respiratory tract infections. symptoms of infection with cowpox virus in humans are localized, pustular lesions generally found on the hands and limited to the site of introduction. the incubation period is 9 to 10 days. the virus is prevalent in late summer and autumn. origin cowpox (variola vaccina) pustules on a cow's udder discovery in the years from 1770 to 1790, at least six people who had contact with a cow had independently tested the possibility of using the cowpox vaccine as an immunization for smallpox in humans. among them were the english farmer benjamin jesty, in dorset in 1774 and the german teacher peter plett in 1791. jesty inoculated his wife and two young sons with cowpox, in a successful effort to immunize them to smallpox, an epidemic of which had arisen in their town. his patients who had contracted and recovered from the similar but milder cowpox (mainly milkmaids), seemed to be immune not only to further cases of cowpox, but also to smallpox. by scratching the fluid from cowpox lesions into the skin of healthy individuals, he was able to immunize those people against smallpox. reportedly, farmers and people working regularly with cattle and horses were often spared during smallpox outbreaks. investigations by the british army in 1790 showed that horse-mounted troops were less infected by smallpox than infantry, due to probable exposure to the similar horsepox virus (variola equina). by the early 19th century, more than 100,000 people in great britain had been vaccinated. the arm-to-arm method of transfer of the cowpox vaccine was also used to distribute jenner's vaccine throughout the spanish empire. spanish king charles iv's daughter had been stricken with smallpox in 1798, and after she recovered, he arranged for the rest of his family to be vaccinated. in 1803, the king, convinced of the benefits of the vaccine, ordered his personal physician francis xavier de balmis, to deliver it to the spanish dominions in north and south america. to maintain the vaccine in an available state during the voyage, the physician recruited 22 young boys who had never had cowpox or smallpox before, aged three to nine years, from the orphanages of spain. during the trip across the atlantic, de balmis vaccinated the orphans in a living chain. two children were vaccinated immediately before departure, and when cowpox pustules had appeared on their arms, material from these lesions was used to vaccinate two more children. in 1796, english medical practitioner edward jenner tested the theory that cowpox could protect someone from being infected by smallpox. there had long been speculation regarding the origins of jenner's variolae vaccinae, until dna sequencing data showed close similarities between horsepox and cowpox viruses. jenner noted that farriers sometimes milked cows and that material from the equine disease could produce a vesicular disease in cows from which variolae vaccinae was derived. contemporary accounts provide support for jenner's speculation that the vaccine probably originated as an equine disease called "grease". although cowpox originates on the udder of cows, jenner took his sample from a milkmaid, sarah nelmes. jenner extracted the pus of one of the lesions formed by cowpox on nelmes to james phipps, an eight-year-old boy who had never had smallpox. he eventually developed a scab and fever that was manageable. approximately six weeks later, jenner then introduced an active sample of the smallpox virus into phipps to test the theory. after being observed for an extended amount of time, it was recorded that phipps did not receive a reaction from it. although jenner was not the first person to conceive the notion of cowpox protecting against the smallpox virus, his experiment proved the theory. it was later discovered that the cowpox vaccination only worked temporarily against the invasion of smallpox and the procedure would need to be repeated several times through one's lifetime to remain smallpox free. in later years, jenner popularized the experiment, calling it a vaccination from the latin for cow, vacca. the amount of vaccinations among people of that era increased drastically. it was widely considered to be a relatively safer procedure compared to the mainstream inoculation. although jenner was propelled into the spotlight from the vaccination popularity, he mainly focused on science behind why the cowpox allowed persons to not be infected by smallpox. the honour of the discovery of the vaccination is often attributed to benjamin jesty, but he was no scientist and did not repeat or publish his findings. he is considered to be the first to use cowpox as a vaccination, though the term vaccination was not invented yet. during the midst of the smallpox outbreak, jesty transferred pieces of cow udder which he knew had been infected with cowpox into the skin of his family members in the hopes of protecting them. jesty did not publicize his findings, and jenner, who performed his first inoculation 22 years later and publicized his findings, assumed credit. it is said that jenner made this discovery by himself, possibly without knowing previous accounts 20 years earlier. although jesty may have been the first to discover it, jenner made vaccination widely accessible and has therefore been credited for its invention. life cycle the genome for the cpxv is over 220kbp. this makes it the largest genome in the orthopoxviral species. it can be divided into three different regions. there are two end regions called r1 and r2 and a main central region that is roughly half of the size of the genome. there are also inverted terminal repeats that are located at the terminal sites of the genome and measure around 10kbp. these inverted terminal repeats can then be divided into two more distinct regions. the first section is around 7.5kbp long and includes a coding region. the other section includes a terminal region that can be repeated up to as many times as thirty and is composed of 50 nucleotides. the cpxv genome encodes only 30-40% of products of which are involved in the pathogenesis of the virus. the cpxv genome has the most complete set of genes out of all of the orthopoxviruses. this unique feature of cpxv makes it ideal to be able to mutate into different strains of the virus. it is a double stranded dna virus. the virus does have an envelope that surrounds the virion. the cowpox's genome allows the virus to encode its own transcription machinery along with its own dna replication machinery. the replication then takes place in the cytoplasm after the virus is in the cell and the virion is uncoated. the virion is then assembled and released from the host cell. the genome is arranged so that both of the ends contain the genes responsible for evading the defenses from the immune system of the host which is only activated in the extracellular portion. these receptors are able to be stopped by cytokine and chemokine secretion by blocking the cytokine and chemokine found extracellularly. this is the process responsible for attachment and entry of the virion into the host cell. because of the large size of the genome, it makes the virus more likely and capable to fight back against the immunes system defenses. out of all of the poxviruses, cpxv has the most cytokine responses that fight back against the immune system. it encodes cytokine receptors such as tnf, crmb, crmc, crmd, and crme proteins. another set of receptors that cpxv have are lymphotoxins such as il-1ß, ifn-y, ifn 1, β-chemokines, and il-18. however, not all of the receptors of cpxv are still not known. cpxv also encodes four tumor necrosis factors (tnf) and lymphotoxin which are the biggest group of homologous receptors for the virus. these receptors play a crucial role that are involved with the immune system. cpxv has two different types of inclusion bodies. all of the poxviruses have basophilic inclusions