Understanding The Coxsackie Virus Biology Essay


Viruses impact public health not only in terms of primary infection but also due to secondary effects on host cells. Complications may become evident months or years after infection and have the potential to be very serious. Coxsackievirus is a species which has the potential to cause complications with a lifetime impact even though primary infection may not be apparent.

Coxsackievirus is a member of the Picornaviridae family and the Enterovirus genus taking its name from the city in New York where it was first isolated in 1948. A group of school-age children in Coxsackie, New York presented polio-like symptoms which were serologically determined to come from a new virus. As a single-stranded plus sense RNA virus it belongs in class IV under the Baltimore classification. Taxonomy of this virus is further divided into groups A and B, each of which contains types. Group A has 24 different types and group B has 6.

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Members of the family Picornaviridae are single-strand plus sense RNA viruses of 7-8 kb pairs which are icosahedral in shape and do not have an envelope. Stability of viral proteins is easier to maintain for naked virions as the reactive lipid envelope is not present to interact with environmental compounds and lead to premature uncoating. Rather than producing their own 5' caps during transcription Picornaviridae use an internal ribosomal entry site (IRES) to take 5' caps from host mRNA. In this way viral proteins are preferentially translated over host proteins. Another interesting fact about Picornaviridae is that a host cell is not required for viral replication. Presented with the proper proteins and other components for cell synthesis in vivo these viruses are able to assemble independently (Shors, 2009).

Once the virion is brought into the host cell and uncoats, a viral polyprotein (VPg) initiates translation of viral RNA. Some of the plus-sense RNA is transcribed into minus-sense RNA to use for genomic replication. The newly translated polyprotein is then broken up into three parts. P1 is further subdivided into three copies of the viral RNA genome. P2 and P3, which contains VPg, are both used to make more viral RNA. Finally, all the RNA is inserted into capsids and new virions are released from the host cell.

A wide range of symptoms are attributed to coxsackievirus infection. One of the more typical displays of this virus is the formation of ulcers at viral replication sites in the mouth (herpangina) and on the palms of the hands. Types A10 and A16 are especially responsible for this and their clinical syndrome is known as hand-foot-and-mouth disease (HFMD). Hoof and mouth disease is commonly confused with this but the diseases are caused by separate viruses which have very specific tropism to either the animal or the human host but not both (CDC, 2010). Fever and rash may accompany these ulcers. Other diseases which can be caused by coxsackievirus include the common cold, meningitis, lung and throat infection (Shors, 2009).

Because coxsackievirus has so many types host immunity cannot prevent spread of the disease. As documented by Osterback, et al. an outbreak in Finland which occurred in the fall of 2008 was caused by a previously unfamiliar type of coxsackievirus called A6. Onychomadesis, or shedding of the fingernails, was the symptom leading to determination that this outbreak was caused by a novel type of coxsackievirus. The authors of that paper believe type A6 may be a major factor in future hand-foot-and-mouth disease outbreaks.

Co-circulation of coxsackievirus A17 with live attenuated polioviruses in vaccine may lead to recombination of the genetic sequence and reactivation of that poliovirus as documented in Madagascar by Jegouic, et al. Related portions of the 3' half of the poliovaccine and CA17 were successfully recombined in a laboratory setting to cause disease in transgenic mice. Poliovirus which is reactivated in this manner is known as pathogenic circulating vaccine-derived poliovirus or cVDVP. This reactivation of previously nonpathogenic poliovirus poses a serious threat to eradication of the disease since previous vaccines will be ineffective against the new strain.

Insulin-dependent diabetes also has links to coxsackievirus since it attacks the β cells in the islets of Langerhans responsible for insulin production. This particular syndrome has significance to me as my sister developed type 1 diabetes after a strong cold. At the time we lived in Fairfax County, Virginia. Unlike many cases of juvenile diabetes which develop during childhood my sister did not develop the disease until her late teenage years.

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In one study conducted by Oikarinen, et al. enterovirus RNA was isolated from the blood of children with type 1 diabetes as well as a control group of children. Children in the diabetic group had a markedly higher incidence of enterovirus RNA in their blood than the children who were able to process sugars normally. Another finding of the study is that boys may be more susceptible to β cell destruction and the subsequent onset of insulin-dependent diabetes than girls.

Another study conducted by Dotta, et al. found coxsackie B4 virus in the pancreatic tissue of insulin-dependent diabetics. The viruses which were extracted were then capable of infecting healthy β cells and causing pyknosis, or the condensation of chromatin in a cell's nucleus as it prepares for apoptosis. Natural killer cells are thought to be the cause of inflammation and destruction of the insulin-producing islet cells.

According to both the CDC and the University of Maryland Medical Center the best prevention for coxsackievirus infection is to avoid infected persons and practice proper handwashing. Children are considered more susceptible than adults due only to lack of previous exposure to the virus. Because the virus may be spread through contact with infected people, fecal-oral contamination, or on fomites daycare centers are especially susceptible and everything must be cleaned in the event of an outbreak to control spread of the disease.

Treatment for coxsackievirus infection is not necessary unless a major complication such as myocarditis develops. Pain from sores inside the mouth may be alleviated using ibuprofen, oral sprays, and gargling with warm salt water. External sores should be kept clean and anyone caring for an individual with hand-foot-and-mouth disease should remain mindful that these sores contain the virus and fluids coming from them can spread the disease.

Immunoglobulin can be used to reduce viral load and inflammation if myocarditis develops. This treatment is well documented in laboratory mice (Takada, Kishimoto, and Hiraoka, 1993) and has been used on humans with some success (Brunetti and Hermes DeSantis, 2008). However, its antiviral properties have not been fully studied in relation to myocarditis because the condition can be caused by factors other than coxsackievirus.

Meningitis is a swelling of the membrane surrounding the brain. Though bacterial meningitis can be treated with antibiotics capable of crossing the blood-brain barrier, an effective method for eliminating viral meningitis from the body has not yet been discovered. Instead bed rest and fluids are recommended to allow the inflammation to subside (CDC, 2010).

Unfortunately the damage caused to the pancreas by this virus is irreversible. Individuals who develop type 1 diabetes due to coxsackievirus must remain on insulin for the rest of their lives. What may seem like a harmless cold or stomach bug has the potential to develop into a serious autoimmune reaction that will change that person's lifestyle. Prevention is very important here since vaccines for this type of coxsackievirus are not currently available. Though this outcome is unlikely it does occur and is not considered rare.

All Enteroviruses are part of the single-stranded plus sense RNA family Picornaviridae. Many share similar symptoms and epidemiology as is the case with poliovirus and coxsackievirus. However, the complications of the two diseases are quite distinct. The most effective way to avoid infection with an Enterovirus is to practice good hygiene and proper handwashing techniques. No vaccines are available for coxsackievirus due to its wide variability. Diabetes, myocarditis, and meningitis are the most serious of the complications which may result from infection and development of vaccines for Group B coxsackieviruses would greatly reduce the incidence and public health impact of these.