Silly Questions???

[Hip]

Do the dsRNA and ssRNA have more of a connection to dengue fever class of pathogens

Dengue is also a virus that definitely forms non-cytolytic infections within cells, comprising ssRNA and dsRNA.

In fact, there was some very interesting research a couple of year ago about the dengue non-cytolytic infection (also called the "defective virus" infection).

This research found that the dengue lytic virus (which the researchers call the "functional virus") and the non-cytolytic virus travel together, and are both transmitted from host to host, and that the non-cytolytic dengue virus ("defective virus") actually helps the lytic dengue virus to spread and create epidemics.


With dengue, you can get a post-infectious fatigue syndrome (see here), and this makes me wonder whether it is the non-cytolytic dengue virus which is causing this fatigue syndrome.

 

[aaron_c]

What we can infer from research though is that a percentage of patients with enteroviral ME do shed virion in their stool

That link won't work for at all (whereas other sci-hub papers will at least give me the abstract). Do you recall the title of the study?

 

[Hip]

That link won't work for at all

The URL sci-hub.io is not presently working, but if you use sci-hub.cc instead, you will get the paper. URLs sci-hub.bz and sci-hub.ac also work.

 

[aaron_c]

Thanks @Hip

It's telling me that the connection is untrusted. Is this to be expected?

 

[Hip]

Is this to be expected?

Yes, it is not a problem.

 

[Janice Hargreaves]

Yes, many people have these viruses, but for reasons unknown, only a small percentage with these viruses develop ME/CFS.

Here are some prevalence rates for common pathogens:

Epstein Barr virus is found in around 90% of adults, 1
HHV-6 is found in nearly 100% of adults (and in 80% of children by 2 years old),
HHV-7 is found in 98% of adults, 1
Chlamydia pneumoniae in 74% of adults, 1
Coxsackievirus B IgM antibodies in 23% of adults in Scotland, 1
Coxsackievirus B3 in 7% of infants in Norway,
Coxsackievirus B4 in 2% of infants in Norway,
Echovirus 9 in 2% of infants in Norway, 1
Cytomegalovirus in 58% of adults, 1
Parvovirus B19 in 61% of adults, 1
Herpes simplex I in 54% of adults,
Herpes simplex II in 16% of adults. 1


Many of these viruses are also linked to other diseases. For example, EBV is linked to multiple sclerosis. Again, it is not known why EBV might possibly be triggering MS in some people, but not in most people.

Note that when we say a pathogen is "linked to" a disease, or "associated with" a disease, this means that statistically, the pathogen is found more commonly in those patients with the disease, compared to how common the pathogen is in the general population. But this association does not prove the pathogen causes the disease (although it's often suspected to be a possible cause).

This may interest you: List of Human Diseases Linked To Infectious Pathogens

This is really fascinating to me. I did a pilot study on beta herpes viruses using the Stanley Neurobiology Foundation brain tissue measuring the viral load using real time qPCR. I found evidence of HHV6A in the cerebellum and an expert told me they thought it could be Purkinje cells which had been infected. There was no evidence of HHV6B, CMV or HHV7. Could it be that that the immune system is using a huge amount of energy to keep these viruses in a latent state? Or do these latent viruses have a means to hijack the energy biosynthesis pathways as they do the DNA biosynthesis systems?

 

[frederic83]

Or do these latent viruses have a means to hijack the energy biosynthesis pathways as they do the DNA biosynthesis systems?

Like the enterovirus, the latent state in tissues where it should not be, is problematic.

 

[Hip]

I did a pilot study on beta herpes viruses using the Stanley Neurobiology Foundation brain tissue measuring the viral load using real time qPCR. I found evidence of HHV6A in the cerebellum and an expert told me they thought it could be Purkinje cells which had been infected.

You were a research scientist in a former life (the former life that all ME/CFS patients have)?

It's interesting that the more neurotropic HHV-6A is more prevalent in ME/CFS. Refs: 1 2

When you look at both HHV-6 and enterovirus (coxsackievirus B and echovirus are the enteroviruses linked to ME/CFS) infections of the CNS, it's typically the astrocytes that are chronically infected, and this astrocyte infection is usually associated with inflammation and/or altered glutamate transporter function, which could in turn cause elevated glutamate in the brain (Dr Cheney thinks elevated glutamate could cause the "wired" symptoms of ME/CFS).

HHV-6 astrocyte infection and altered glutamate transporter function: refs: 1 2
Coxsackievirus B astrocyte infection and altered glutamate transporter function: refs: 1 2

Like the enterovirus, the latent state in tissues where it should not be, is problematic.

There is some research that partial reactivation of herpes viruses could be the problem in some ME/CFS patients:

Epstein-Barr virus partial reactivation refs: 1 2

Dr Kazuhiro Kondo has a theory that partial reactivation of HHV-6 may cause ME/CFS, as well as depression and bipolar disorder. Ref: 1

The idea is that in partial reactivation, some viral proteins can be manufactured in the cell (which may alter cellular function), but without full viral particles being made.

Analogously in chronic enterovirus infections, non-cytolytic enteroviruses can exist as a low level smoldering infection within cells.

 

[Janice Hargreaves]

All this lovely info is brilliant.! Thank you for sharing.
Yes I was a research Biomed scientist pre ME/CFS.
One of my mentors was an Immunology prof and his pet theory was about Immunsenescence caused by CMV where the thymus has been over run by commited T cells?. I'm not convinced. I feel the range of HHVs, sites of latency and viral loads are the problems.
I have the sense that when I try to use too much energy on whatever talking, thinking, moving then I get the poisoned feeling back which I had years ago with IM. The sites of pain are generally the same places. Could this be re-emergence of some latent virus since the body hasn't the energy to keep it latent? Could swabs of sore throats quantify viruses and compare to when not sore? Could by using other body fluids like tears, saliva and CSF be screened for evidence of range of viruses being controlled by looking at the various latent membrane proteins (LMP1 and LMP2?) . I am sure this has already all been done but I can't seem to find much.
I know from reading work by Ablashi (the HHV6 expert) that EBV can transactivate other HHVs.
In the UK I cannot seem to be able to get to see an Immunologist or a Virologist who is interested in ME/CFS. Doh!
Any other helpful pointers would be great. Thank you again.

 

[Hip]

Could this be re-emergence of some latent virus since the body hasn't the energy to keep it latent?

A lot of the early research on ME in the 1980s and 1990s found enterovirus infection in the muscles. Enterovirus, EBV and HHV-6 seem to be the main viral associations of ME/CFS. I guess it's possible that use of the muscles during physical exercise could create an upsurge in viral replication in the muscles. At one point I was looking into the cytokine IL-6 as a possible explanation for PEM, because huge amounts of IL-6 are generated during exercise (IL-6 is considered both a cytokine and a myokine), but I did not get very far with that idea.

Could by using other body fluids like tears, saliva and CSF be screened for evidence of range of viruses being controlled by looking at the various latent membrane proteins (LMP1 and LMP2?) .

That is an interesting idea. I have not heard of tears and saliva being used to detect viruses, but it sounds feasible. For enteroviruses though, you find very few viral particles in the blood and CSF of ME/CFS patients, because in chronic enterovirus infections, the virus lives in the tissues, and often inside human cells as an intracellular infection (search these forums for "non-cytolytic enterovirus" for more details).

So in ME/CFS patients with chronic enterovirus infections, PCR of blood samples may often come back negative due to the low level of viral particles in the blood. For ME/CFS, you usually use plaque reduction neutralization testing or micro-neutralization testing to measure antibody levels in the blood. More info here. Enterovirus expert Dr John Chia uses such neutralization tests for his ME/CFS patients. He also uses a more sensitive staining test (immunohistochemistry) on stomach biopsy samples from ME/CFS patients, to detect tissue infection with enterovirus.

The neutralization tests that Dr Chia uses are available at ARUP Lab, but the tests are very expensive, $440 I believe for the coxsackievirus B neutralization test, and the same for the echovirus neutralization test (these are the two enterovirus species linked to ME/CFS).

I am also in the UK, and there no neutralization tests that I am aware of in the UK or Europe. Though ArminLabs do a cheap test (€68) for coxsackievirus, but I am not sure how its sensitivity compares to the neutralization test.


Testing for EBV and HHV-6 is more straightforward in ME/CFS, because the antibody tests offered by most labs are sensitive enough to detect these.

You may be interested in this document that I slowly complied, which gives some details about pathogen testing in ME/CFS:

Chronic Fatigue Syndrome — A Roadmap For Testing And Treatment

How long have you had ME/CFS, by the way?

 

[Janice Hargreaves]

More lovely details! Brilliant. Thank you for sharing!
I've had this diagnosis since 2000.
I wonder if they could use a radionucleotide tag to a common epitope for the HHVs and then use fMRI to scan for places and get a rough quantity indicator of viral load? I saw somebody on Horizon TV programme (I think at UCL?) had done this with early Alzheimers to visualize the amyloid tangles in living brains. So surely they could design a tag for the latent viruses?
Yes thank you, I have looked at the Roadmap for testing but feel my GP would be very reluctant to get those tests done since their view seems very much to be "What's the point of testing, if we can't treat you?" I had a real struggle to get my Vit D tested. He even questioned why I would want it. When I reminded him of all the aches etc, then he no longer resisted. Came back at 29.
Many thanks again for all this interesting stuff. I do find this whole thing tickles my curiosity.

 

[parabola]

I seem to remember that with EBV, you are better to be exposed as a child as the Illness is milder, people getting infected for the first time as adults are more likely to get post viral complications, which has certainly been my experience.

 

[Hip]

I wonder if they could use a radionucleotide tag to a common epitope for the HHVs and then use fMRI to scan for places and get a rough quantity indicator of viral load? I saw somebody on Horizon TV programme (I think at UCL?) had done this with early Alzheimers to visualize the amyloid tangles in living brains. So surely they could design a tag for the latent viruses?

Coincidentally enough, I think along the same lines recently. In one of the brain autopsies performed on an ME/CFS patient, they used a stain which marks the VP1 capsid protein of enterovirus, and found enterovirus in some of the glial cells. I was wondering whether you could radio label such a stain and then inject it.

Yes thank you, I have looked at the Roadmap for testing but feel my GP would be very reluctant to get those tests done since their view seems very much to be "What's the point of testing, if we can't treat you?"

Yes I had the same issues with my NHS GP. I had to press him for basic tests such as hypothyroidism and anemia, which should be ruled out before you settle on an ME/CFS diagnosis.


Have you tried any of the regular treatments used by ME/CFS patients and ME/CFS doctors, such as vitamin B12 injections, low-dose naltrexone, the methylation protocol, oxymatrine (in the case of enterovirus infections)?