Mitochondrial localization of viral proteins as a means to subvert host defense

[natasa778]

http://medicalxpress.com/news/2012-05-nervous-viruses-sabotage-cell-hijack.html

To spread, nervous system viruses sabotage cell, hijack transportation

Herpes and other viruses that attack the nervous system may thrive by disrupting cell function in order to hijack a neuron's internal transportation network and spread to other cells.

Princeton University researchers made the first observation in neurons that common strains of the herpes virus indirectly take control of a cell's mitochondria, the mobile organelles that regulate a cell's energy supply, communication with other cells, and self-destruction response to infection. The team reports in the journal Cell Host and Microbe that viral infection elevates neuron activity, as well as the cell's level of calcium — a key chemical in cell communication — and brings mitochondrial motion to a halt in the cell's axon, which connects to and allows communication with other neurons.

The authors propose that the viruses then commandeer the proteins that mitochondria typically use to move about the cell. The pathogens can then freely travel and reproduce within the infected neuron and more easily spread to uninfected cells. When the researchers made the mitochondria less sensitive to calcium the viruses could not spread as quickly or easily.

 

[natasa778]

p.s. not sure about ME (is there any research, anyone?) but it is know that in autism there IS neuronal mitochondria calcium overload. The mitochondria is just not handling calcium well - they looked for genetic reasons but could not find any, as usual...

 

[mellster]

Very interesting find - thx! Maybe that could explain mitochondrial weakness/exhaustion proportional to viral load.

 

[Enid]

Thanks natasha - growing body of evidence of viruses and the nervous system.

 

[alex3619]

This is very very interesting to me. I have an hypothesis called I suppose the citrate hypothesis. It remains unproven and still lacks decent evidence. However it predicts two things. The first is that there will be elevated intracellular ionized calcium spikes, rather than constant elevated calcium (actually the early version was constant, but I modified it). The second is that the citrate is used to flush the cell at night. The reason for this is to flush the mitochondria of toxic metals (which I called the citrate flush hypothesis) - I postulated it was a defence mechanism to deal with high iron and other metals, triggered primarily by excessive oxidative stress. The problem is the cause, in this case, is not metals, and so the flushing never succeeds. These calcium spikes are why we have abnormal acetylcholine reactions (according to my model, this is not fact).

Now of course I am wondering if my model fits in with herpes virus infections? What makes this complicated is that citrate flushes out ionized calcium too, but also triggers increased calcium surges (hence spikes) when there is a calcium inducing stimulus.

Bye, Alex

 

[heapsreal]

This is very very interesting to me. I have an hypothesis called I suppose the citrate hypothesis. It remains unproven and still lacks decent evidence. However it predicts two things. The first is that there will be elevated intracellular ionized calcium spikes, rather than constant elevated calcium (actually the early version was constant, but I modified it). The second is that the citrate is used to flush the cell at night. The reason for this is to flush the mitochondria of toxic metals (which I called the citrate flush hypothesis) - I postulated it was a defence mechanism to deal with high iron and other metals, triggered primarily by excessive oxidative stress. The problem is the cause, in this case, is not metals, and so the flushing never succeeds. These calcium spikes are why we have abnormal acetylcholine reactions (according to my model, this is not fact).

Now of course I am wondering if my model fits in with herpes virus infections? What makes this complicated is that citrate flushes out ionized calcium too, but also triggers increased calcium surges (hence spikes) when there is a calcium inducing stimulus.

Bye, Alex

Calcium can have alot to do with cardiac arrythmia's, is this what dr lerner is finding in his cfs/ebv patients, abnormal t-waves and t-wave inversion???? Maybe this is why he also uses a holter monitor to help diagnose his patients??

cheers!!!

 

[natasa778]

Could this be related?

http://www.ncbi.nlm.nih.gov/pubmed/7968720

It is suggested that chronic fatigue syndrome/fibromyalgia is caused by virus injury to the calcium channels leading to larger quantities than usual of calcium ions entering the striated muscle cells. Should this be true, then treatment with a calcium antagonist (CA) may possibly be of value.

...
In our opinion the calcium channels of the striated
muscle cells in CFS are injured so that an increased
amount of calcium is permitted to enter the
cells. This would result in increased muscular tone,
so much so, that the individual cells, as well as the
muscle as a whole, develop a state comparable to
that following static muscular work. This injury to
the calcium channels of the cell wall may be caused
by viral infection (1,10,12). The fact that virus infection
is able to injure striated muscle cells is seen
in epidemic pleuradynia (Bomholm disease) (10,ll);
further, it has been reported that there are histological
abnormalities in muscles of patients with certain types
of fibrositis and that this may result from virus infection
(12). Swartz (1) has suggested that viral infection
may increase muscle proteolysis and Arnold et al (15)
have theorized that excessive glycolytic activity may
be the explanation of the CFS in their patients. If
these hypotheses are correct, then treatment with a
calcium antagonist or calcium channel blocker could
possibly lead to an improvement in the patient’s condition.
This led us to attempt treatment of a patient
who undoubtedly suffered from CFS with a calcium antagonist
and we take the liberty of reporting such a case.....

 

[natasa778]

also in the same paper:

Treatment with a CA was started on 15 March 1991.
We employed isradipine (9) (lomir) tablets of 2.5 mg.
1.25 mg were given as a test dose, this was increased
after 2 days to 1.25 mg four times per day. This
dosage was further increased after 5 weeks to 1.25
mg t.i.d. and 3.5 mg h.s., and from 21 October 1991
she took 1.25 mg at noon, 1.25 mg at 6p.m. and a
5mg capsule of Lomir Retard h.s.
The patient felt better 4-5 days after the start of
treatment and her condition improved dramatically
during the following 5 weeks of treatment, inasmuch
as she was able at this time to sleep for up to 6 hours
per night, only waking up l-3 times per night. However,
her condition varied considerably from day to
day (this may be due to the fact that the patient, due
to the improvement in her condition was inclined, despite
being a physician, to over-exert herself). These
bouts of recurrence became more seldom after increasing
the dosage and gradually the patient was able
to resume a normal physical life.
An attempt was made to discontinue the treatment
some 10 weeks after initiation, but the patient resumed
treatment due to recurrence of all the symptoms
after 3-4 days. This again resulted in a gradual
improvement and she reached status quo after roughly
10 days....

 

[alex3619]

Hi natasa778, thank you for these two comments. It could indeed be related though of course it would require some good research to prove it. What I find interesting here is the description of the muscle damage. I have muscle pain that is related to static mucle stress - if my muscles are active for too long, statically, then the pain sets in and continues to worsten. Furthermore this pain does not go away very quickly. As a result of continued muscle stress in the mid to late 1980s I was in constant severe pain till early to mid 2000s at which point due to careful pacing and who knows what else the pain began to decline. It comes back though in any muscle which has static load. Bye, Alex

PS I did a quick search of Bornholme Disease and its suggested it might be linked to Coxsackie B virus, which I have had. It is however a very short disease, lasting a week, I do wonder if ME or CFS might be in some cases a form of chronic Bornholme Disease. Certainly I have had all the symptoms of this disease - and many of us have according to my experience. In particularly we get the unspecified severe chest pain.

 

[mellster]

Very interesting indeed. I wonder whether increased calcium spill could also cause localized calcification and what can be perceived as trigger points, rib/chest wall pain and generalized fibro knots pain? This would at least mean that St Amand was not totally off base with his FM hypothesis

 

[heapsreal]

Hypocalcaemia
ECG changes include:

• Intermittent QT prolongation, or intermittent prolongation of the QTc (corrected QT interval) on the EKG (electrocardiogram) is noted. The implications of intermittent QTc prolongation predisposes to life-threatening cardiac electrical instability (and this is therefore a more critical condition than constant QTc prolongation). This type of electrical instability puts the patient at high risk of torsades de pointes, a specific type of ventricular fibrillation which appears on an EKG (or ECG) as something which looks a bit like a sine wave with a regularly increasing and decreasing amplitude. (Torsades de pointes, as with any type of ventricular fibrillation, causes death, unless the patient can be electrically cardioverted, and returned to a normal cardiac rhythm.)

This is info i have found on how low and high calcium levels affect cardiac muscle by showing changes in ecg's. I would like to know if lerner thinks the ecg changes he sees in me/cfs patients with herpes viruses are related to levels of calcium?? I guess changes in skeletal muscles would also be abnormal as well.
http://en.wikipedia.org/wiki/Hypocalcaemia
http://en.wikipedia.org/wiki/Hypercalcaemia
i know they are wiki links but this info is quite general easily found elsewhere.

cheers!!!

 

[mellster]

Would be interesting to know how many though actually have this as a proven symptom. I had normal serum calcium levels everytime I was tested and all the ecgs/ekgs and stress tests were fine (thankfully). However I used to eat a super calcium-rich diet (never broke a bone despite crazy skiing accidents etc. and everybody comments on how heavy my bones are) and I wonder whether soft tissue calcification can be responsible for some of the inflammatory pain, esp. around the 'trigger points'. I also have adjusted my diet since.

 

[alex3619]

Hi Mellster, you could have severe localized hypo- or hyper-calcemia and have totally normal serum calcium. This is because it looks like the calcium balance is disturbed inside selected cells (which was a feature of my early model). I suspect its possible to have normal serium calcium, high calcium in some cells, and low calcium in others, though it would probably be rare to find this. Serum calcium is only a guide. Which cells? Those affected by whatever is disturbing the tissues - at least nerves and the linings of blood vessels from what I am reading, but its early in this research and the whole story could change as more is discovered.

It may also be possible that I have been wrong about infection/disturbance in blood vessel linings, and these are disturbed by abnormal calcium in the nerves that regulate vascular tone. In other words it might affect nerves everywhere.

In the case of coxsackie virus you also have to consider muscle - this may also be one more reason why so many of us get muscle cramps .

Bye, Alex

 

[mellster]

Thanks Alex, yeah, the old problem that serum levels are not necessarily indicative of what's going on inside cells/tissue. While I do think that the general inflammation mostly comes from cytokines/gut, I have noticed a certain stiffness and some tender/trigger on the torso that differ from the general inflammation and have been wondering whether calcium/calcification plays a role but that's only one possibility - besides getting old But I am missing a certain fluidity I once had and it its hard to describe as I have always been a bit clumsy and heavy bone-wise. But to illustrate I always had a slipping rib but it was hardly noticeable as the cartiledge and tissue seemed to be well "lubricated" but now I can feel it more often and it seems to be rubbing harder against the cartiledge when popping in an out. Anyhow, I am digressing, one possible mostly side-effect free calcium antagonist could be guaifenesin for people to try if not tried yet. cheers

 

[girlinthesnow]

I have both chronic hypocalcaemia and chronic viral (herpes) infections.

I just found this old thread about calcium/hypocalcaemia and viral hijacking of cell mechanism.

Is there any new research into this mechanism?

Thanks!