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- 1. Introduction<br />Coxsackie B virus, a category of Coxsackie Viruses is the causative agents of many illnesses ranging from gastrointestinal dysfunction to viral myocarditis, myocarditis being the focus of this discussion. The prevalence of Coxsackie B virus is not well known but figures from WHO state that Coxsackie B virus accounted for 11.9% of all enteroviruses in the United States during 2001-2. Viral myocarditis is an inflammatory disease of the heart, whereby heart cells are infected and then later destroyed by the immune system, thus destroying the heart. Myocarditis predominantly affects men around the age of 42, so a vaccine/treatment needs to be designed.<br />Disease Mechanism<br />1084580122555<br />Figure 1: Complexed DAF/CAR important factor for CVB import<br />Upon infection which is usually the faecal-oral route, the virus will gain entry and infect heart cells. Cardiomyocytes express cell surface receptors which are important for heart muscle development but which are also complimentary to the coxsackie B virus (CVB). These receptors are CAR (coxsackievirus-adenovirus receptor) and DAF (decay-accelerating factor). According to Selinka HC et all 2003, these proteins form an association through non-covalent bonds which enables CVB to interact with the complex and then internalise the virion (figure 1). Internalisation triggers virion unfolding which allows viral RNA translation via host machinery hijacking. Knowlton Ku (date unknown) describes how CVB’s once in the cytosol of myocytes can produce proteases which cleave specific proteins, including dystrophin, this cleavage has been suggested to be a factor in viron release from myocytes. Myocarditis is the result of the infection, but more specifically is the result of inflammation of the heart tissue by the immune system. The mechanism of which the immune system responds to the infection is suggested by Christopher C Kemball et al 2011. It is suggested that a receptor TLR-8 can recognise ssRNA and signal to the immune system that foreign bodies have gained access to the cell. The innate immune system then destroys the infected cell. If many heart cells have been infected, then it is likely that the immune system will destroy many of these cells, leading to heart failure. It is evident that the myocyte cell surface harbours very important receptors for the entry and detection of CVB. <br />Future Directions<br />Further studies should be directed towards the proteases which are involved in dystrophin cleavage, as this has been suggested to be a main factor in virion release. If these proteases can be targeted, then virion release may be impaired, whilst still flagging the cell for destruction, just not in dangerous numbers. Therefore the two questions needing to be addressed are 1) What is/are the specific protease(s) involved in dysrtophin cleavage and 2) Can viral proteases be targeted with a vaccine? Answering these questions would be a major advancement in understanding the mechanism in which CVB spreads in a cellular manner and this in turn would bring us closer to a CVB vaccine/drug.<br />References<br />Selinka HC, Wolde A, Sauter M, Kandolf R, Klingel K, Virus-receptor interactions of coxsackie B viruses and their putative influence on cardiotropism, http://www.ncbi.nlm.nih.gov.proxy.library.adelaide.edu.au/pubmed/12920584 <br />Figure 1 accessed from Text above<br />Knowlton KU, CVB infection and mechanisms of viral cardiomyopathy. http://www.ncbi.nlm.nih.gov.proxy.library.adelaide.edu.au/pubmed/18357777<br /> Kemball CC, Alirezaei M, Whitton JL, Type B coxsackieviruses and their interactions with the innate and adaptive immune systems. http://www.ncbi.nlm.nih.gov.proxy.library.adelaide.edu.au/pubmed?term=Type%20B%20coxsackieviruses%20and%20their%20interactions%20with%20the%20innate%20and%20adaptive%20immune%20systems<br />