PERSISTENT MUMPS INFECTION AND ABNORMAL ION CHANNEL FUNCTION: CFIDS/ME IMPLICATIONS
By Alan Cocchetto, Medical Director, NCF©2007
With the NCF's (National CFIDS Foundation) research moving ahead, I have elected to look at several topics that will be up for discussion. In this column, I will be examining the concept of persistent mumps infection. I will also be taking a look at abnormal ion channel function in CFIDS/ME as it relates to a potential persistent mumps-like infection (ie. - Parainfluenza Virus-5 infection). Hopefully, the reader will be able to see some of the basic framework that is beginning to emerge as a result of dissecting this small segment of the disease process.
Let's first take a scientific look at another rubulavirus
that is very familiar and recognizable to most people.
I am talking about the mumps virus. Much like Parainfluenza
Virus-5 that has been identified in patients with CFIDS/ME
[1,2,3,4], PIV-5 is classified as a rubulavirus as is
mumps. Both viruses are members of the larger parainfluenza
Among RNA viruses that are known to persist in the human central nervous system (CNS), members of the parainfluenza (paramyxovirus) family are the most prominent. Both the measles virus as well as the mumps virus has been implicated in chronic neurological disease associated with persistent infections of the CNS. In fact, the mumps virus is the single most common cause of meningitis and encephalitis. However, various neurological symptoms, including ataxia and psychological disorders, can follow acute infections and have been reported to be associated with elevated mumps virus antibody titers in the cerebrospinal fluid years after the infection. The scientific literature suggests that the long term effects of mumps virus infection could be due to irreversible brain damage following acute infection or to a chronic infectious process. Is this a far fetched idea? Hardly. Other members of the parainfluenza family cause persistent infections of the brain. Canine distemper virus and the measles virus are examples here. Both of these viruses persistently infect neural cells and therefore alter their neural function. Years ago, I remember reading in Hilary Johnson's acclaimed book, Osler's Web, the possibility that CFIDS/ME was an infectious disease of the brain. Well, let me now state that a persistent rubulavirus infection that invades the CNS would certainly satisfy this observation!
Two researchers from the University of Minnesota's School of Medicine have closely examined persistent mumps virus infected cells. Dr. Richard Ziegler and Dr. Edward Stauffer found that persistent infection by the mumps virus induced alterations in cellular excitation. This cellular excitation was due to alterations or changes in the sodium channels. Ziegler and Stauffer found that such virus-altered action potentials led to a disruption of normal synaptic transmission in neural pathways affected by infected neurons. Thus, normal integrative processes were affected and this led to serious neurophysiological dysfunction.
Persistent mumps virus infection directly affects the
sodium channels but spares the calcium and potassium channels.
The authors concluded that "the viral effect is a
specific rather than a general one with the sodium channel
being particularly susceptible." What would cause
these types of changes in the sodium channel by the mumps
virus you might ask? The authors suggest that specific
viral proteins associated with the mumps virus itself
are directly responsible for this effect.
Next, I want to examine a research paper written by Chaudhuri et. al. in 2000 . The title of this paper is "The symptoms of chronic fatigue syndrome are related to abnormal ion channel function." In this paper, the authors explore the pathogenesis of chronic fatigue syndrome and write "In the early 1960s, it was recognized that nearly 5% of victims of acute ciguatera poisoning did not recover for many months or years due to a chronic disabling syndrome with persistent fatigability and weakness. Chronic ciguatera poisoning is an important consideration in the differential diagnosis of anyone presenting with chronic fatigue or in whom the diagnosis of CFS is being considered in certain parts of the world. Ciguatoxins (CTXs) are heat stable, non-protein, lipophilic toxins produced by a dinoflagellate (Gamberdiscus toxicus) associated with dead coral and algae which can be passed up the food chain to result in sporadic human outbreaks. They comprise a group of unique heterocyclic molecules that include some of the most potent ion-channel altering substances. CTX-1 is the most potent sodium channel toxin known and is the major toxin in ciguateric fish. CTX bind sodium channel receptors in both somatic and autonomic nerves in the open mode, producing a prolonged sodium channel activation. Symptoms arise from the semi-permanent opening of the sodium channels, explaining the phenomenon of paradoxical temperature sensation, a sensation which is commonly reported by most CFS patients. CTX also include a sleep-inducing fraction (<1% of total toxicity) and hypersomnolence is a typical symptom of ciguatoxicosis and CFS....CTX, which can lead to CFS symptoms, block sodium channels in the open mode causing entry of sodium into neural tissues and muscles. This ingress of sodium is followed by water which in turn, leads to swelling of neural tissues, a phenomenon observed both electrons microscopically and by laser scanning microscopy with volume measurements calculated by three-dimensional volume reconstruction. It is postulated that chronic effects of CTX at the molecular and osmostic level (intracellular edema) can account for at least some of the subjective symptoms of lethargy, weakness and easy fatiguability. If this is correct, then it follows that some of the symptoms of CFS might be due to ion channel abnormalities involving neural and skeletal muscle tissues." Chaudhuri et. al. state that "Circumstantial evidence supports the concept of an acquired channelopathy in CFS."
The NCF is of the opinion that the observations by Chaudhuri et. al. are in agreement with the research generated by Dr. Hokama who has provided evidence for the presence of ciguatoxin-reactivity in patients with chronic fatigue syndrome and whose function acts to alter the sodium channels in this disease . Furthermore, the evidence provided herein supports the notion that rubulavirus infections directly target the sodium channels through an interaction with virus specific proteins. Preliminary research supports the role for PIV-5 targeted sodium channel alterations and therefore functions. Such changes, as outlined above, are associated with the symptoms of CFIDS/ME.
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