Have you considered the implications of these two studies finding an interation between Adenovirus and Enterovirus for explaining the mysterious cases of acute flaccid myelitis, especially since adenovirus is associated with cold-like symptoms?
Together they appear to illustrate a generalized phenomenon that might be occurring in present day paralysis cases, involving simultaneous infection with these two types of viruses.
Regards,
Eli Kammerman
Polyradiculoneuritis in children groups during simultaneous circulation of enteroviruses and adenoviruses.
Zentralbl Bakteriol Mikrobiol Hyg A. 1985 Nov;260(3):387-95.
Abstract
Two cases of polyradiculoneuritis in children were noted during January, 1984. Each girl was a member of a different group of children: the first group was newly constituted of children from various remote regions of Czechoslovakia in a Medical Institution, the second one included children attending the same nursery school for a long time. In both groups, all or most of the children went through one or two respiratory infections which preceded the development of a paralytic disease. From the first girl, coxsackievirus A9 was recovered in nasopharyngeal swabs and in a stool sample. Among contacts in the Children's Medical Institution, a concurrent circulation of this enterovirus and of an adenovirus type 3 was demonstrated by isolation attempts and confirmed by serological examinations. From the second girl, coxsackie A9 and an adenovirus type 29 were demonstrated in the same stool sample and a simultaneous circulation of both virus species among the nursery school and family contacts was proved by isolation attempts and by serological investigations. The concurrent, overlapping or sequential circulation of adenoviruses and enteroviruses may perhaps contribute to a compromised immunity resulting in a manifestation of paralysis.
PMID: 3004069
Adenovirus type 21-associated acute flaccid paralysis during an outbreak of hand-foot-and-mouth disease in Sarawak, Malaysia.
Clin Infect Dis. 2003 Mar 1;36(5):550-9. Epub 2003 Feb 14.
Abstract
We report the virological and clinical features of 8 children who presented with adenovirus-associated acute flaccid paralysis (AFP) during an epidemic of enterovirus type 71 (EV71)-associated hand-foot-and-mouth disease (HFMD) in Sarawak, Malaysia, in 1997. Neutralization tests and phylogenetic analysis revealed adenovirus type 21 (Ad21), although DNA restriction digests suggested that this virus was different from the prototype Ad21. Four children had upper-limb monoparesis, 2 had lower-limb monoparesis (one of whom had changes in the anterior spinal cord noted on magnetic resonance imaging), and 2 had flaccid paraparesis. At follow-up, 4 children were noted to have made full recoveries and 3 had residual flaccid weakness and wasting. Neurophysiological investigation revealed a mixture of axonal and demyelinating features in motor and sensory nerves, with denervation. These findings suggest that Ad21 might cause AFP by anterior horn cell damage or neuropathy of the brachial or lumbosacral plexus. The occurrence of these unusual adenovirus infections during an outbreak of EV71-associated HFMD suggests that an interaction between the 2 viruses may have occurred.
PMID: 12594634
Eli, Thanks for the question. I have had little time for contemplation! I wrote the article in summer session between years of medical school, and am furiously working toward finishing residency so I may then jump back in to research, while also having patient contact.
I think there are several viruses involved in the spectrum of presentation of Alzheimer's. I think the easiest one to find/prove will be HSV1, but I think other viruses may impact the HSV1 sub-clinical encephalopathic progress of HSV1 infection on multiple levels.
Thanks for asking! I would love to hear more and see more work in the field!!
Jim
Reasonable explanation of higher susceptibility of younger children to AFM from enterovirus infection in 2008 reference below by Ahn and Lee due to higher number of CAR receptors available to bind to the virus and internalize it.
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Second reference below by Patzke and Rathgen from 2010 provides insight on the consequences of CAR receptors being overloaded by virus and unable to fulfill their purpose of ensuring neurite extension and adhesion to extracellular matrices, potentially explaining AFM as "lost connections" between motor neurons.
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Primary neurons become less susceptible to coxsackievirus B5 following maturation: the correlation with the decreased level of CAR expression on cell surface.
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J Med Virol. 2008 Mar;80(3):434-40.
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Ahn J, Jee Y, Seo I, Yoon SY, Kim D, Kim YK, Lee H.
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- ... In contrast to immature neurons, mature neurons were less susceptible to CVB5 infection, as indicated by the decrease of cytopathic features.
- In mature neurons, progeny virus production was significantly hindered, and virus capsid protein VP1 synthesis and virus genome amplification were concomitantly reduced.
- In addition, the expression of coxsackievirus and adenovirus receptor (CAR), the major receptor of CVB5, was down-regulated in mature neurons. ...
- These findings demonstrate that mature neurons become less susceptible to CVB by the decrease of CAR level. Thus, the data strongly support the idea that the level of virus receptor in neurons is one of the crucial determinants in the age-dependency of CVB virulence in central nervous system.
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The coxsackievirus-adenovirus receptor reveals complex homophilic and heterophilic interactions on neural cells.
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J Neurosci. 2010 Feb 24;30(8):2897-910.
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Patzke C, Max KE, Behlke J, Schreiber J, Schmidt H, Dorner AA, Kröger S, Henning M, Otto A, Heinemann U, Rathjen FG.
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- ...Blocking antibodies were found to inhibit neurite extension in retina organ and retinal explant cultures, whereas the application of the recombinant fiber knob of the adenovirus subtype Ad2 or extracellular CAR domains promoted neurite extension and adhesion to extracellular matrices.
- We observed a promiscuous interaction of CAR with extracellular matrix glycoproteins...
- The membrane proximal Ig domain of CAR, termed D2, was found to bind to a fibronectin fragment, including the heparin-binding domain 2, which promotes neurite extension of wild type, but not of CAR-deficient neural cells.
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