Human coxsackievirus 12066 Coxsackie virus is a member of the Picornaviridae family of viruses in the genus termed enterovirus. Coxsackie viruses are subtype members of enterovirus that have a single strand of ribonucleic acid (RNA) for its genetic material. The enteroviruses are also referred to as picornaviruses (pico means "small," so, "small RNA viruses"). Coxsackie virus was first isolated from human feces in the town of Coxsackie, New York, in 1948 by G. Dalldorf. Coxsackie virus is also written as coxsackievirus in some publications. Coxsackie viruses are separable into two groups, A and B, which are based on their effects on newborn mice (Coxsackie A results in muscle injury, paralysis, and death; Coxsackie B results in organ damage but less severe outcomes.) There are over 24 different serotypes of the virus (having distinct proteins on the viral surface). Coxsackie viruses infect host cells and cause host cells to break open (lyse). Type A viruses cause herpangina (painful blisters in the mouth, throat, hands, feet, or in all these areas). Hand, foot, and mouth disease (HFMD) is the common name of this viral infection. Coxsackie A 16 (CVA16) causes the majority of HFMD infections in the U.S. It usually occurs in children (age 10 and under), but adults can also develop the condition. This childhood disease should not be confused with the "foot and mouth disease" usually found in animals with hooves (for example, cattle, pigs, and deer). Type A also causes conjunctivitis (inflammation of the eyelids and white area of the eye). Type B viruses cause epidemic pleurodynia (fever, lung, and abdominal pain with headache that lasts about two to 12 days and resolves). Pleurodynia is also termed Bornholm disease. There are six serotypes of Coxsackie B (1-6, with B 4 considered by some researchers as a possible cause of diabetes in a number of individuals). Both types of viruses (A and B) can cause meningitis, myocarditis, and pericarditis, but these occur infrequently from Coxsackie infections. Some researchers suggest Coxsackie virus (mainly Coxsackie B4) has a role in the development of acute onset type I (formerly known as juvenile) diabetes, but this relationship is still under investigation. Coxsackie viruses and other enteroviruses may cause the childhood disease of hand, foot, and mouth disease. However, the majority of children with Coxsackie virus infections completely resolve the symptoms and infection in about 10-12 days. Recently (July 2012), in Asia (particularly Cambodia), children suspected to be infected with enterovirus 71 had a 90% mortality. This epidemic (mainly in babies, toddlers, and children under 2 years of age) is still under intense investigation and it is likely researchers will have a better understanding of this high death rate linked to enterovirus 71 soon. If enterovirus 71 is ultimately found responsible for these deaths, it is likely the virus has developed a new lethal ability to rapidly infect and destroy children's lung tissue. However, the research is ongoing and some investigators suggests that the children are dying from a combination of enterovirus 71, Streptococcus suis, and dengue viral coinfections (MedicineNet - Coxsackievirus). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 Coxsackievirus DNA vaccine pCMV/VPl encoding VP1 VO_0004361 DNA vaccine Research pIRES [Ref2260:Henke et al., 2004] Intramuscular injection (i.m.) IL-2 (Henke et al., 2004) Intramuscular injection (i.m.) DNA vaccine construction Vector pIRES expressed major structural protein (capsid protein VP1) VP1 of coxsackievirus B3 (CVB3) (Henke et al., 2004). VO_0000286 DNA immunizations with the major structural protein VP1 of coxsackievirus B3 (CVB3) have been previously found to protect mice from a lethal challenge with CVB3. Co-expression of the immune-stimulatory interleukin-2 (IL-2) can increase the efficacy of the inoculated DNA vaccine depending on the route of administration and the mouse strain used. After i.m. administration, IL-2 co-expression increased the protection rate by 18.3% whereby the g.g. inoculation was much less effective in BALB/c mice. In contrast, after g.g. inoculation IL-2 co-expression increased the protection rate by 36.7% whereby the i.m. was much less effective in C57BL/6 mice (Henke et al., 2004). Coxsackievirus Inactivated Vaccine CV-A5 Inactivated or "killed" vaccine Research Intraperitoneal injection (i.p.) Vero cell-adapted CV-A5 strain is a promising vaccine candidate and could be used as a multivalent HFMD vaccine component in the future. (Jin et al., 2021) In an outbreak of HFMD in Xiangyang, China, in 2017, rectal swabs from patients were obtained. CV-A5-3487 was isolated in both RD and Vero cells and grown to titers higher than 1 × 10^8 50% cell culture infectious doses (CCID50)/ml. A Vero cell isolate, CV-A5-vN20, was selected as a vaccine candidate. Vero cells in a 10-layer cell factory were infected with CV-A5-vN20 at a multiplicity of infection (MOI) of 0.001. The harvest was purified through two steps of ultracentrifugation. (Jin et al., 2021) Intraperitoneal injection (i.p.) Coxsackievirus A5 (Jin et al., 2021) Levels of NtAb titers in sera on days 0, 14, and 28 were determined, representing those of preimmunization, postboost, and postchallenge antisera. In suckling mice, NtAbs were detectable only after boosting (day 14), and the seroconversion rate was 100%. NtAb titers increased dramatically after challenge (day 28, P < 0.001), reflecting strong immune responses following challenge. The results demonstrated that NtAb levels correlated with the survival of immunized mice, and there were no differences in titers of different antigen groups. (Jin et al., 2021) A group of 3-day-old mice were primed and boosted on day 10 through the i.p. route (Jin et al., 2021) All mice in the immunized groups survived after 14 days of observation, showing 100% protection, while all mice in the mock-immunized group died at 6 days postchallenge. (Jin et al., 2021) A group of 3-day-old mice were challenged 4 days later (once antibody levels had increased) with CV-A5-M14 at a dose of 10 LD50 (2 × 10^6 CCID50/mouse). (Jin et al., 2021) licensed Coxsackievirus infection human vaccine Generic Unknown VO_0001228 Inactivated or "killed" vaccine Licensed A generic representation of vaccines utilized to prevent human coxsackievirus infection, most commonly employing inactivated (killed) virus preparations to induce protective immunity. These vaccines are designed to elicit an immune response without causing disease. VP1 Human coxsackievirus B3 254973291 CDD:278501 CDD:119412 12072 ? VP1 8.88 29963.04 335 picornavirus capsid protein; pfam00073 >ACT98478.1 VP1, partial [Coxsackievirus B3] GPVEDAVTAAIGRVADTVGTGPTNSEAIPALTAAETGHTSQVVPGDTMQTRHVKNYHSRSESTVENFLCR SACVYFTEYENSGSKRYAEWVVTTRQAAQLRRKLEFFTYIRFDLELTFVITSTQQPSTTQNQDAQILTHQ IMYVPPGGPVPDKVDSYAWQTSTNPSVFWTEGNAPPRMSIPFLSIGNAYSNFYDGWSEFSRNGVYGINTL NNMGTLYARHVNTGSTGPIKSTIRIYFKPKHVKAWIPRPPRLCQYEKAKNVNFQPSGVTTTRQSITAMTN TGAF Protective antigen Henke et al., 2004 journal Henke A, Chiang CS, Zell R, Stelzner A 2004 64 2 131-136 Antiviral research MedicineNet - Coxsackievirus website http://www.medicinenet.com/coxsackie_virus/article.htm