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HHV-6 researcher Dr Bhupesh Prusty also finds "something in the serum" of ME/CFS patients

Hip

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Fluge and Mella in 2016 showed that when myoblast cells (young muscle cells) from healthy people were exposed to the blood serum of ME/CFS patients, the cells developed energy metabolism abnormalities.

That suggested that there is "something in the serum" of ME/CFS patients which is amiss, because even when healthy cells come into contact ME/CFS patients' serum they develop energy metabolism issues.

Prof Ron Davis also found evidence that something in the serum is affecting ME/CFS patients cells (see this thread).



@Cort's latest blog from the NIH ME/CFS Conference II details the work of German HHV-6 researcher Dr Bhupesh Prusty, who is now the third scientist to find "something in the serum" in ME/CFS patients.

Dr Prusty's has previously found that HHV-6 reactivation in cells changes mitochondrial structure and function.

But intriguingly, Prusty's research suggests this not only happens in HHV-6-infected cells, but even in healthy cells by some unknown mechanism or factor that remotely alters the mitochondria in uninfected cells as well (some info here).



Prusty's latest finding is that this mitochondrial-altering factor transmits via the blood serum, because when he added ME/CFS patients' serum to healthy cells, their mitochondria began to break up.

And when he added to healthy cells the supernatant (liquid) taken from a HHV-6 infection in cell culture, this also caused the same changes in the mitochondria.

And then removing removing ME/CFS patients’ serum from the cells caused the mitochondria to return to a healthy state again.

Prusty is now attempting to isolate this mitochondrial inhibiting factor from the serum. He is using the exosomes that Maureen Hanson is examining in her NIH research center.


Some articles about Dr Prusty's work:
SMCI 2016 RAMSAY TEAM 5 RESEARCH UPDATE
HHV-6 MEDIATED MITOCHONDRIAL MODULATION AND ITS ASSOCIATION TO ME/CFS
 
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junkcrap50

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Fantastic news. Glad another person besides Ron Davis is looking for the "something in the blood." Are Fluge & Mella also trying to identify the "something"? I haven't heard anything about them persuing this line of research.

Prusty is now attempting to isolate this mitochondrial inhibiting factor from the serum. He is using the exosomes that Maureen Hanson is examining in her NIH research center.
What does this mean? How does using exosomes help isolate the inhibiting factor? Is he just trying to find a match to the inhibiting factor?

EDIT: I'm aware of what exosome are and what they do. But Hip's and Cort's sentences about using exosomes is too matter of fact and vague.
 
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Hip

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I don't know that much about it, but exosomes are tiny vessels that provide a means of cell-to-cell communication, so I presume Dr Prusty thinks his mitochondrial inhibiting factor might be transported within these exosomes.
 
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Exosomes come from inside the cell. Specifically, from the multivesicular body (MVB). The MVB can contain coxsackie viruses according to this paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993817/

What if the only viruses in our blood are hidden inside exosomes and so cannot easily be found?

They are, let's say, absorbed by another cell and a range of immune and metabolic alterations is set in train, including mitochondrial fission.
 

Hip

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They are, let's say, absorbed by another cell and a range of immune and metabolic alterations is set in train, including mitochondrial fission.
As I understand it, I believe Dr Bhupesh Prusty is proposing that some factor (such as an immune signaling molecule) may be transmitted from HHV-6-infected cells to uninfected cells, and it is this factor which he thinks may be causing the uninfected cells to also develop mitochondrial alterations.

This factor appears to exist in the serum, and may or may not be inside exosomes.
 
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Dr Bhupesh Prusty, who is now the third scientist to find "something in the serum" in ME/CFS patients.
I believe that Karl Morten was the third scientist to find "something in the serum" in ME/CFS patients. This is slide 44 showing the result of his muscle cell experiment from his New Zealand presentation at the end of last year.
KarlMortenPlasmaSwap.JPG

Exciting times. I was impressed by the out of box thinking of these scientists - I hope Karl Morten and Bhupesh Prusty can get funding to continue their search for the "something" in the blood.
 

junkcrap50

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I believe that Karl Morten was the third scientist to find "something in the serum" in ME/CFS patients. This is slide 44 showing the result of his muscle cell experiment from his New Zealand presentation at the end of last year.
Exciting times. I was impressed by the out of box thinking of these scientists - I hope Karl Morten and Bhupesh Prusty can get funding to continue their search for the "something" in the blood.
Do you know of Dr. Morten is pursuing identifying the "something in the blood" that he's discovered? Need as many hands on deck in trying to ID it since it's seems to be confirmed by now 4 researchers.
 

Wally

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Does anyone happen to know if the “something” that Hanson, Prusty and/or Morten have seen in the serum of ME/CFS patients may be a “particle” in the same size range as Ron Davis is investigating?
 
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Hip

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Nice summary of the four studies which have found "something in the serum (or in the plasma)" here.


Note that plasma is obtained by allowing a blood sample to stand in a test tube for an hour, such that the cells clump together and fall the bottom of the tube. The pale yellow liquid that collects above these clumped cells is the plasma. Plasma is 90% water.

Thus plasma is the blood with the red cells and white cells removed. But plasma still contains the clotting factors which are present in the blood.

Serum is the plasma with the clotting factors removed.

Plasma and serum are very similar.
 
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I’m just trying to figure out how platelets are looked at in this type of research. I’m confused by what I’m reading, and now I’ve been reading too long, to me it sounds like plasma is contaminated by platelets but at low concentrations (they centrifuge which removes most of the platelets). Serum is free of platelets. PBMCs are free of platelets. So it’s just whole blood samples that contain platelets?

This is just gathered from various google sources and I’m really unsure.

So when Prusty was looking at the blood clot section and found the hhv6 RNA sequence in 40% of patients, was he looking at platelets? Or not neseccarily because there’s a mix of cells?

Platelets seem interesting for a lot of reasons, including the sticky blood observation and how they can be involved in viral defence or used and manipulated by viruses.
 

Annikki

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Prusty's latest finding is that this mitochondrial-altering factor transmits via the blood serum, because when he added ME/CFS patients' serum to healthy cells, their mitochondria began to break up.

Prusty is now attempting to isolate this mitochondrial inhibiting factor from the serum. He is using the exosomes that Maureen Hanson is examining in her NIH research center.
Do you think this mitochondrial inhibiting factor might be related to this?
Apoptosis-inducing factor

From Wikipedia: https://en.wikipedia.org/wiki/Apoptosis-inducing_factor
Crystallographic structure of the human apoptosis inducing factor (rainbow color cartoon diagram, N-terminus = blue, C-terminus = red).[1]
Identifiers Symbol AIFM1Alt. symbols PDCD8NCBI gene 9131HGNC 8768OMIM 300169RefSeq NM_004208UniProt O95831Other data Locus Chr. X q25-q26
Apoptosis inducing factor is involved in initiating a caspase-independent pathway of apoptosis (positive intrinsic regulator of apoptosis) by causing DNA fragmentation and chromatin condensation. Apoptosis inducing factor is a flavoprotein.[2] It also acts as an NADH oxidase. Another AIF function is to regulate the permeability of the mitochondrial membrane upon apoptosis. Normally it is found behind the outer membrane of the mitochondria and is therefore secluded from the nucleus. However, when the mitochondrion is damaged, it moves to the cytosol and to the nucleus. Inactivation of AIF leads to resistance of embryonic stem cells to death following the withdrawal of growth factors indicating that it is involved in apoptosis.[2][3]
Function
Apoptosis Inducing Factor (AIF) is a protein that triggers chromatin condensation and DNA fragmentation in a cell in order to induce programmed cell death. The mitochondrial AIF protein was found to be a caspase-independent death effector that can allow independent nuclei to undergo apoptotic changes. The process triggering apoptosis starts when the mitochondria releases AIF, which exits through the mitochondrial membrane, enters the cytosol, and finally ends up in the cell nucleus where it signals the cell to condense its chromosomes and fragment its DNA molecules in order to prepare for cell death. Recently, researchers have discovered that AIF's activity is dependent upon the type of cell, the apoptotic insult, and its DNA-binding ability. AIF also plays a significant role in the mitochondrial respiratory chain and metabolic redox reactions.[4]
Synthesis
The AIF protein is located across 16 exons on the X chromosome in humans. AIF1 (the most abundant type of AIF) is translated in the cytosol and recruited to the mitochondrial membrane and intermembrane space by its N-terminal mitochondrial localization signal (MLS). Inside the mitochondria, AIF folds into its functional configuration with the help of the cofactor flavin adenine dinucleotide (FAD).
A protein called Scythe (BAT3), which is used to regulate organogenesis, can increase the AIF lifetime in the cell. As a result, decreased amounts of Scythe lead to a quicker fragmentation of AIF. The X-linked inhibitor of apoptosis (XIAP) has the power to influence the half-life of AIF along with Scythe. Together, the two do not affect the AIF attached to the inner mitochondrial membrane, however they influence the stability of AIF once it exits the mitochondria.[4]
Role in mitochondria
It was thought that if a recombinant version of AIF lacked the first N-terminal 120 amino acids of the protein, then AIF would function as an NADH and NADPH oxidase. However, it was instead discovered that recombinant AIF that do not have the last 100 N-terminal amino acids have limited NADP and NADPH oxidase activity. Therefore, researchers concluded that the AIF N-terminus may function in interactions with other proteins or control AIF redox reactions and substrate specificity.
Mutations of AIF due to deletions have stimulated the creation of the mouse model of complex I deficiency. Complex I deficiency is the reason behind over thirty percent of human mitochondrial diseases. For example, complex I mitochondriopathies mostly affect infants by causing symptoms such as seizures, blindness, deafness, etc. These AIF-deficient mouse models are important for fixing complex I deficiencies. The identification of AIF-interacting proteins in the inner mitochondrial membrane and intermembrane space will help researchers identify the mechanism of the signaling pathway that monitors the function of AIF in the mitochondria.[4]
Isozymes
Human genes encoding apoptosis inducing factor isozymes include:

Evolution
The apoptotic function of AIFs has been shown in organisms belonging to different eukaryotic organisms including mentioned above human factors: AIM1, AIM2, and AIM3 (Xie et al., 2005), yeast factors NDI1 and AIF1 as well as AIF of Tetrahymena. Phylogenetic analysis indicates that the divergence of the AIFM1, AIFM2, AIFM3, and NDI sequences occurred before the divergence of eukaryotes.[5]
Role in cancer
Despite an involvement in cell death, AIF plays a contributory role to the growth and aggressiveness of a variety of cancer types including colorectal, prostate, and pancreatic cancers through its NADH oxidase activity. AIF enzymatic activity regulates metabolism but can also increase ROS levels promoting oxidative stress activated signaling molecules including the MAPKs. AIF-mediated redox signaling promotes the activation of JNK1, which in turn can trigger the cadherin switch.[6][7][8][9]