Journal of IiME Volume 3 Issue 1 www.investinme.org Human enteroviruses and chronic infectious disease (continued) disease, the long-term persistence of a slowly replicating HEV can lead to cell damage, due to the virus' own enzymes it uses to replicate, and this damage eventually impacts the function of the organ (the heart) itself. Another chronic disease that is closely linked to HEV infections is type 1 (insulin dependent) diabetes (or T1D)(15, 30). Type 1 diabetes occurs due to an inability to control glucose metabolism which is an outcome from the loss of insulin-producing beta cells in the pancreatic Islets of Langerhans(17). Although some cases are thought to be due only to a specific expression of individual genetic traits, most T1D cases cannot be so easily explained and therefore, environmental factors (like infections) have been sought to explain how T1D is initiated(1, 20). One environmental factor that is high on any list, are the HEV: many clinical observations and experimental studies implicate HEV as agents that can and do trigger T1D onset in humans(15, 30). While CVB have been associated with T1D cases, other non-CVB HEV have also been implicated in T1D onset, further adding to the evidence for a role of HEV in T1D onset. At present, it is unclear whether the HEV involved persists in the host after the initial infection that sets the disease in motion, or whether it is more of a classical HEV acute infection, one that is rapidly cleared by the immune response. What is very clear, however, is that CVB can rapidly trigger T1D onset in a T1D-prone mouse called the NOD mouse if the mouse is already prediabetic from its own autoimmune attack on its pancreatic islets(14). This means that under certain circumstances (when one has autoimmune insulitis present, and one is infected with an HEV against which one has no pre-existing protective immunity, and it is the correct HEV at the right dose), T1D in humans could likely be initiated by an HEV infection. Using the rapid onset model in mice to make inferences for humans, we would predict an HEV infection that rapidly kills enough beta cells will initiate T1D. However, the virus infection might not accomplish this: the virus might instead kill insufficient numbers of beta Invest in ME (Charity Nr. 1114035) cells for T1D to ensue. What then? This is where the autoimmune (in which one's immune system attacks oneself) aspect of T1D sets this disease apart from the previously discussed chronic heart disease. In T1D, enough insulin-producing beta cells must be destroyed in order for T1D to occur: this can happen by autoimmune processes, by virus attack, or both occurring together. We are currently assessing whether longterm persistence of HEV is a factor in both the NOD mouse model of T1D and in human beings. Chronic fatigue syndrome and the link to HEV infection In a paper that received much notice, Chia and Chia showed that HEV RNA and protein were detectable in the great majority of stomach biopsy tissue samples from patients diagnosed with chronic fatigue syndrome (CFS) but only in few biopsy samples from control patients without the disease(9). This report has suggested that a commonly circulating human virus group might be a primary etiologic agent involved in CFS, a disease that is marked by a difficult diagnosis and a near complete lack of understanding about what agent(s)/mechanism(s) trigger the disease. As we have seen from the previous discussion, HEV may be able to initiate a disease process just from an acute infection, which is then resolved, or from a continuing infection as well, involving a persistent virus population. Persistence is, however, a relative term. In an immunologically-normal individual, i.e., one who is able to mount normal vigorous immune responses against infectious agents, an HEV infection may be able to persist via a TD genome mechanism for some weeks, perhaps months, but eventually will be eradicated by the immune response. Thus, such infections are temporary (unlike herpesviruses or HIV). Although HEV are common viruses, the very high positive correlation with the CFS stomach samples was surprising. In other known associations of HEV with human Page 28/76
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