Discovery Offers Possible Treatment for Viruses Linked to Chronic Fatigue Syndrome

[shannah]

http://chronicfatigue.about.com/b/2...iruses-linked-to-chronic-fatigue-syndrome.htm

Discovery Offers Possible Treatment for Viruses Linked to Chronic Fatigue Syndrome
Tuesday July 13, 2010
Research Brief

Researchers believe they've discovered the way herpes viruses invade cells -- something that had long remained a mystery. The new study, published in Nature Structural & Molecular Biology, provides what they say is a detailed map of the herpes virus "cell-entry machinery." Researchers believe this finding could lead to new antiviral drugs that are effective against the family of viruses.

Three of the 8 herpes viruses are suspected of being tied to chronic fatigue syndrome. They are human herpesvirus 6, Epstein-Barr virus and cytomegalovirus.

Any potential drug therapies resulting from this work are likely many years away.

http://www.ncbi.nlm.nih.gov/pubmed/20601960

Nat Struct Mol Biol. 2010 Jul;17(7):882-8. Epub 2010 Jul 4.

Crystal structure of the conserved herpesvirus fusion regulator complex gH-gL.
Chowdary TK, Cairns TM, Atanasiu D, Cohen GH, Eisenberg RJ, Heldwein EE.

Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.

Abstract
Herpesviruses, which cause many incurable diseases, infect cells by fusing viral and cellular membranes. Whereas most other enveloped viruses use a single viral catalyst called a fusogen, herpesviruses, inexplicably, require two conserved fusion-machinery components, gB and the heterodimer gH-gL, plus other nonconserved components. gB is a class III viral fusogen, but unlike other members of its class, it does not function alone. We determined the crystal structure of the gH ectodomain bound to gL from herpes simplex virus 2. gH-gL is an unusually tight complex with a unique architecture that, unexpectedly, does not resemble any known viral fusogen. Instead, we propose that gH-gL activates gB for fusion, possibly through direct binding. Formation of a gB-gH-gL complex is critical for fusion and is inhibited by a neutralizing antibody, making the gB-gH-gL interface a promising antiviral target.

PMID: 20601960 [PubMed - in process]


Publication Types, Secondary Source ID, Grant SupportPublication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Secondary Source ID:
PDB/3M1C
Grant Support:
1DP20D001996/DP/NCCDPHP CDC HHS/United States
AI056045/AI/NIAID NIH HHS/United States
AI076231/AI/NIAID NIH HHS/United States
AI18289/AI/NIAID NIH HHS/United States
RR-15301/RR/NCRR NIH HHS/United States
LinkOut - more resources

 

[leelaplay]

http://chronicfatigue.about.com/b/2...iruses-linked-to-chronic-fatigue-syndrome.htm

Discovery Offers Possible Treatment for Viruses Linked to Chronic Fatigue Syndrome
Tuesday July 13, 2010
Research Brief

Researchers believe they've discovered the way herpes viruses invade cells -- something that had long remained a mystery. The new study, published in Nature Structural & Molecular Biology, provides what they say is a detailed map of the herpes virus "cell-entry machinery." Researchers believe this finding could lead to new antiviral drugs that are effective against the family of viruses.

Three of the 8 herpes viruses are suspected of being tied to chronic fatigue syndrome. They are human herpesvirus 6, Epstein-Barr virus and cytomegalovirus.

Any potential drug therapies resulting from this work are likely many years away.

http://www.ncbi.nlm.nih.gov/pubmed/20601960

PMID: 20601960 [PubMed - in process]

Thanks Shannah

I wish I were one of our science brains. However, I'm not. And therefore not sure about my idea that one possibility of "the cause" of ME/CFS is perhaps

a) having a genetic disposition (Kerr's gene work),
b) perhaps something that lowers the immune system, including stress
and then c) exposre to a virus or retrovirus that sends the body's neuro immune systems cascadingly out of whack, then affecting all the rest of the body's systems.

Treatment of the virus being effective for treating ME/CFS I guess would depend on whether the virus continues to play an active part in sending the body's systems haywire.

But no matter what - just knowing that research is progressing in this way is exciting.

 

[Dolphin]

a) having a genetic disposition (Kerr's gene work)

Just a note to point out that nearly all of Kerr's published gene work is on gene expression which is not to do hereditary factors per se (although gene expression like pretty much anything one measures, probably has a hereditary component).

 

[ukxmrv]

(just a short and probably unimportant note)

Kerr is going to be doing work on SNP's. Someone pointed this out to me on another thread as I had only heard of his gene expression work.

Too soon to tell of course if it will tell us anything useful.

 

[richvank]

Hi, Shannah.

Thank you for posting this!

The gB that is mentioned in this abstract is glycoprotein B. Here is some other information about it, that I think is very interesting. A few years ago, Palamara et al. at the University of Rome published a paper about herpes simplex I, the virus that resides in nerve cells and produces cold sores when it flares. They found that glutathione suppresses the activation of this virus. The mechanism is that when there is sufficient glutathione in the cell, and the proper high ratio of reduced to oxidized glutathione, this suppresses the formation of cystine disulfide bonds in glycoprotein B. Unless these bonds form, the new virions cannot fully develop their outer coats and cannot propagate to other cells.

Glycoprotein B is found in all the human herpes viruses. Therefore, I think it is reasonable to suspect that normal levels of glutathione suppress activation of all the human herpes viruses, and is one of the important mechanisms that normally keeps them in their latent state.

I think this is consistent with the observation that reactivation of herpes simplex I to produce cold sores occurs when the person has had a lot of exposure to ultraviolet light from the sun. That is known to promote oxidative stress and therefore to deplete glutathione, which is the basis for the body's antioxidant enzyme system.

Another example is that the activation of the herpes zoster (varicella zoster) virus to produce shingles (in a person who has had chicken pox earlier in life and thus has this virus in its latent state in their nervous system) often occurs when the person has been subject to a lot of stress, which also depletes glutathione.

It seems reasonable to me to believe that glutathione depletion in the particular cell types where the other herpes family viruses reside (HHV-6, EBV and CMV) will also allow reactivation of these viruses. That's why I have suggested in the Glutathione Depletion--Methylation Cycle Block hypothesis for CFS that the reason these viruses are commonly reactivated in CFS is that glutathione is depleted.

For more information on this, please see www.cfsresearch.org clicking first on CFS/M.E. and then on my name.

Best regards,

Rich

 

[richvank]

(just a short and probably unimportant note)

Kerr is going to be doing work on SNP's. Someone pointed this out to me on another thread as I had only heard of his gene expression work.

Too soon to tell of course if it will tell us anything useful.

Hi, ukxmrv.

I'm happy to hear this, and I hope he is able to go ahead with it. I met him at the 2007 IACFS conference, and I urged him to study polymorphisms instead of gene expression, because I believe it will be more fruitful in figuring out the pathophysiology of CFS. He told me then that he was planning to do this, but this was three years ago.

Best regards,

Rich

 

[leelaplay]

Just a note to point out that nearly all of Kerr's published gene work is on gene expression which is not to do hereditary factors per se (although gene expression like pretty much anything one measures, probably has a hereditary component).

thanks Dolphin. This is another eg of how trying to absorb new info while being cognitively-challenged ends up with me not getting the correct info or full-picture. Argghhh - very humbling for someone who used to be able to think.

ps - did I notice that I contributed to your new name? A well merited appelation.

 

[Dolphin]

(just a short and probably unimportant note)

Kerr is going to be doing work on SNP's. Someone pointed this out to me on another thread as I had only heard of his gene expression work.

It could have been me. But in the context of what was said, it was useful to point out that (virtually) all of his published research was on gene expression, not hereditary factors (SNPs, etc).

 

[Dolphin]

thanks Dolphin. This is another eg of how trying to absorb new info while being cognitively-challenged ends up with me not getting the correct info or full-picture. Argghhh - very humbling for someone who used to be able to think.

Lots and lots of people, including doctors, get it wrong.
I remember watching an MEA video of Dr. Gow explaining his gene expression research and the paeditrician (Patel? some Indian/South Asian name anyway) then mentioned about Dr. Gow's research and hereditary (i.e. he got it wrong even after the talk!). So with so many people being confused, some of these will then go on to confuse others! I'm reading the Cartoon Guide to Genetics at the moment to get a start on biology as I stopped studying biology at 16. Some people on the forum definitely have an advantage on some issues. Most of the mathematics I studied e.g. pure math, doesn't help me much!

ps - did I notice that I contributed to your new name? .

My memory is not the best so can't really remember.

A well merited appelation.

I'll take that as a compliment.

Much better than what Cort said to me after I changed from Ill since 1989 (which I had for a few minutes/hours):
I like Dolphin much better. Maybe it'll start a string of fish names - that would be nice.
- talk about an insult.