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Viruses use 'fake' proteins to hide in our cells.

Ema

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Viruses use 'fake' proteins to hide in our cells
Date:
July 7, 2014

Source:
Monash University

Some viruses can hide in our bodies for decades and make 'fake' human proteins that trick our immune cells into believing nothing is wrong. Now researchers at the Imaging Centre of Excellence at Monash and Melbourne Universities have determined the basic structure of one of the two known families of these deceptive proteins.

Using synchrotron light on a common virus that lives in people happily and for the most part harmlessly, they have worked out the structure of the fake proteins. The research, published online by the Journal of Biological Chemistry, is an important first step towards producing better vaccines and drugs to fight viral disease.

The research team focused on the structure of m04 immunoevasin from mouse cytomegalovirus, a member of the m02 protein family. Cytomegaloviruses belong to the herpes virus family, which can cause glandular fever, chicken pox and cold sores. About half the population become infected with the virus, develop flu-like illness and then carry the virus for life. But the virus can be dangerous to pregnant women and people whose immune system becomes suppressed.

Monash University's Dr Richard Berry, a senior author of the paper, said the discovery was important for understanding how this family of viruses can hide from our immune systems.

"Our work highlights how these viruses mimic the immune system in order to evade it," Dr Berry said.

Immune T-cells patrol our bodies checking on the health of cells. One of the things they look for is a complex of proteins on the surface of cells. This major histocompatibility complex (MHC) presents a snapshot of what's inside the cell. If bits of viral protein are detected by the T cells, they flag the infected cell for destruction.

Viruses fight back by disrupting the production of the MHC protein complex, thus reducing the numbers on the outer membrane.

But then, the next stage of what could be described as an evolutionary arms race kicks in. If there are too few MHC proteins on the outer membrane of a cell, then a different type of immune cell, termed the natural killer cell, will kill the cell just to be safe.

Cytomegaloviruses have responded to this by making large families of fake cellular proteins that interfere with natural killer cell recognition. It is the basic structure of one of these families the researchers have revealed for the first time.

Professor Jamie Rossjohn, the other senior author and a Chief Investigator of the Imaging Centre, leads the research group.

"It's been a race against our international competitors which we won with the help of the Australian Synchrotron. We were only able to produce very small protein crystals from which to solve the structures -- too small to allow us to gain meaningful data with anything other than synchrotron X-rays," Professor Rossjohn said.

Story Source:

The above story is based on materials provided by Monash University. Note: Materials may be edited for content and length.

Journal Reference:

  1. R. Berry, J. P. Vivian, F. A. Deuss, G. R. Balaji, P. M. Saunders, J. Lin, D. R. Littler, A. G. Brooks, J. Rossjohn. The Structure of the Cytomegalovirus-Encoded m04 Glycoprotein, a Prototypical Member of the m02 Family of Immunoevasins. Journal of Biological Chemistry, 2014; DOI: 10.1074/jbc.M114.584128
 

heapsreal

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I dont have a link but remember that herpes viruses had a way to lower our natural interferon levels and this was the possible reason for low nk function in some cfs/me people and how these viruses can avoid our immune system.
Interesting, most are infected with these viruses but maybe we should be looking for the people who have those mechanisms in place for these viruses to avoid the immune system??

Thats why i think if someone is positive to any of the herpes viruses and shows low nk function then a trial of antivirals is worth a shot??
 

NK17

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592
Very interesting @Ema, thanks for posting it.

@heapsreal I'm entering my 5th month on Valcyte, I have every possible known human herpes virus IgG titers super high and super low NK cells' function, still no improvement ...

I'm thinking to restart Famvir, which I took for 9 months, back when I was more functional.

A little try with an A/V cocktail is worth a try, don't you think so?
 

heapsreal

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Very interesting @Ema, thanks for posting it.

@heapsreal I'm entering my 5th month on Valcyte, I have every possible known human herpes virus IgG titers super high and super low NK cells' function, still no improvement ...

I'm thinking to restart Famvir, which I took for 9 months, back when I was more functional.

A little try with an A/V cocktail is worth a try, don't you think so?


There have been people use valcyte which helped hhv6 and cmv but needed to add famvir or valtrex to lower ebv. Adding famvir is worth a shot as it seems to have some effect on all the herpes viruses.

Also think an immune mod to help increase nk function is needed. Not just immunovir but also look into cycloferon and arbidol/ arbivir? ? These immune mods are interferon inducers so work against herpes viruses which try to turn down our own interferon production.

Also consider If your not getting results from avs and your sure the viruses are an issue, maybe you have an ongoing bacterial infection. This is something Dr Lerner has found in his research.

If enteroviruses u think could be an issue than immune mods will help with this as well as herpes viruses.
 

Gingergrrl

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@heapsreal I will not know my test results of which viruses I have or my NK functioning for two weeks (although I know I have high EBV titers from test earlier this year from my ND.)

I have never taken any anti-virals (except natural ones) and am extremely sensitive to meds and side effects. From your experience if it turns out I do not have CMV, which a/v do you think is the best to start with?
 

heapsreal

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@heapsreal I will not know my test results of which viruses I have or my NK functioning for two weeks (although I know I have high EBV titers from test earlier this year from my ND.)

I have never taken any anti-virals (except natural ones) and am extremely sensitive to meds and side effects. From your experience if it turns out I do not have CMV, which a/v do you think is the best to start with?


I'm partial to famvir as it has effect on most herpes viruses to certain degrees and did help me with cmv. It's also quite safe long term and is used long term as suppression therapy for other herpes viruses. Dose seems to vary amongst many who have used it. I find 250mg twice a day effective and have used higher doses with no obvious benefits over the lower doses. A common dose though seems to be 500mg twice a day. So depends on cost? ?

its a long term treatment though antivirals and months before one notices any improvement, so it can be costly and is hit and miss. Also for many on valcyte improvements can occur after one stops treatment, this i think because valcyte can also suppressbone marrow production and lower white cell counts. So always a good option to swap over to famvir if one uuses valcyte.

for some getting these viruses down allows immune system to regenerate but for some of us our immune system stays down so need to stay on antivirals and or immune mods.

Those of us who respond are a specific subset. I don't think antivirals are an effective treatment for everyone with cfs/me as I think the main issue we have are immune dysfunction. I think what separates us all are what infections we have????

after saying all that, if your lucky enough to be in the herpes sub group than there's possible treatments.
 

Gingergrrl

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@heapsreal when you say you are partial to Famvir is that b/c it worked best for you of the things you tried? Do you think it is good for ANY herpes virus?

I realize after my appt that I have so many more questions for the doctor but I guess I really need to wait to see which viruses I actually have and what he recommends for me.

Are Valtrex, Famvir & Valcyte all taken in pill form? Also, is Valcyte the only one that requires weekly labs or do all three?
 

NK17

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Messages
592
@Gingergrrl43 my experience was first with Famvir, which I took for 9 months at a fairly high dose in order to try to pass the BBB (blood brain barrier) and didn't need to have frequent safety labs.

Now I've been on Valcyte for 5 months and apart from the first month of weekly safety labs, if you start with the loading dose, you just need your blood to be drawn once a month.

I've never had any major reaction to drugs. As a teenager I was treated with antibiotics for several months for toxoplasmosis. I'm alive tanks to my mom and grandma sixth sense, as a child they took me to the ER, against my pediatrician's will, a chest x-ray showed scarring in my lungs due to mycoplasma pneumoniae. I was lucky in that they gave me a brand new antibiotic. I think I am a PWME who needs to treat infections that my otherwise dysfunctional immune system is not able to fight or keep under control.

Too bad I had to live with my faulty immune system since I was born and wait 30 years before I had a diagnosis of full ME (through the CCC and ICC).

We need to keep in mind that we're all different and have different pathogens playing havoc on us, but if you have a good ME/CFS doctor who is willing to try to help you, my suggestion is that you should give any of the appropriate treatment a try.

If you can't tolerate the treatment you can always stop. Now this is my personal experience and my very personal opinion.
 

Gingergrrl

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@NK17 Thank you for all the info and you have given me a lot to think about. I wish I knew my test results now but in the scheme of things two more weeks is not too long to wait. I will be having lots more questions for you guys at that time!
 

NK17

Senior Member
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592
@NK17 Thank you for all the info and you have given me a lot to think about. I wish I knew my test results now but in the scheme of things two more weeks is not too long to wait. I will be having lots more questions for you guys at that time!
Yes @Gingergrrl43 two weeks might seem an eternity, but they'll go by quickly enough and you'll have your test results and we'll be happy to chime in, share anecdotes and experiences and support you.

I remember how impatient I was too three summers ago. I can still feel that mix of incertitude that in the end I might not have ME/CFS and a gut feeling telling me that indeed that's what I had been suffering with and that finally I had found a doctor who tried to understand me and my condition.
 

heapsreal

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@heapsreal when you say you are partial to Famvir is that b/c it worked best for you of the things you tried? Do you think it is good for ANY herpes virus?

I realize after my appt that I have so many more questions for the doctor but I guess I really need to wait to see which viruses I actually have and what he recommends for me.

Are Valtrex, Famvir & Valcyte all taken in pill form? Also, is Valcyte the only one that requires weekly labs or do all three?

Firstly i have ebv/cmv. I used famvir first and after 12 months on famvir i was functioning better then at any stage so far since having cfs. Due to cost i changed to valtrex and went back to square one within a few months and also labs i have done worsened also. SO valtrex wasnt for me. I went back on famvir and improved but not to where i was prior. I then did about 18months on valcyte and improved some more with it. Im currently on famvir and about every 4 weeks i stop famvir to see where im at and to see if the immune mods have improved my immune function enough to handle the viruses themselves. SO far i last about 2-4 weeks off av's before needing to go back on them, only started doing this, this year. I have been on antivirals since 2009?

So im partial to famvir because it initially worked quite well for me, even though its not suppose to work on cmv, but they cant prove it doesnt? There has been a few who have had improvement with famvir who had cmv and hhv6, so it can help. It might be all one needs without having to pay the cost of valcyte or increased side effects, i guess its a gradual step and only move to valcyte if u need to.

Hind sight is a great thing. Knowing what i know now i would have stayed on famvir longer and tried to increase immune function before considering coming off antivirals. But i only had access to nk function testing only a short while i was in a research study, so i dont really have this option anymore but can get nk numbers tested which are in the low normal. If they increase though i guess its a guide.

Valcyte is said to have better penetration of the nervous system then famvir but i havent seen anything in black and white, though i think valcyte is stronger but has increased risks/side effects. Liver and kidney function lab work needs to be done more regularly with valcyte, initially its done more frequently and then length of time between labs is increased. After the initial stages i was getting labs every 3 months for this. Also need full blood count to keep an eye on white blood cell counts/neutrophils etc as valcyte can suppress bone marrow which is where these cells come from. I did end up with neutropenia from valcyte and bad sinus infections from this that were only eased with constant antibiotics. Since stopping valcyte and using immune mods my sinus infections have gone, so far and neutrophils have come up. So your doc needs to keep an eye on these. This was one of the reasons why i stopped valcyte but i now think it was time to stop anyway.

Famvir and valtrex i would consider getting a liver/kidney function test after 3 months?? and then every 12 months?? but if your getting other labs done more frequently then get them done then also. A doctor should know this really but then many dont?

Also when i first started antivirals, many protocols only lasted 6-12months but now i think its something that we might have to stay on for atleast a few years. Valcyte 6-12months and then maintained on something like famvir.

I dont want to say its a cure all as its a big comittment cost wise and time wise and u can be on them for 6 months plus and then realise it hasnt helped(could be a few reasons for this though), so i dont want to pump this up and someone to get disappointed after investing so much into this treatment, i guess be prepared for the worst and hope for the best. But if your in the right sub group then you can improve your function alot. I just dont think anyone can say definately that its going to help but use testing as an educated guess. Also many of us who have improved with antivirals have also kept trying other treatments etc like balancing hormones, antioxidants etc etc

I hope this has helped, if u want to pm me happy to try and answer your questions.
 

Gingergrrl

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@heapsreal thank you so much for all the info and I will definitely PM you once I am back home and when I get the test results.

My gut instinct is to start with Famvir both due to the cost and the potential side effects of Valcyte. I apologize for repeating this question but are both pill form (not injections, etc?)

Also, you mentioned that if someone is in the "right sub group" that the av's can really help which is basically what the specialist told me. Can you explain how it is determined what subgroup someone is in? Is it by which viruses you have?

For example (and I don't know yet in my case) but if someone has EBV and HHV-6 but not CMV is that a distinct subgroup?

Also which immune modulators did you take with Famvir? I got the sense that the specialist I saw does not do immune modulators but I could be wrong about this and need to check my notes which are in my suitcase. I think they can cause autoimmunity in some people?
 

Gingergrrl

Senior Member
Messages
16,171
Yes @Gingergrrl43 two weeks might seem an eternity, but they'll go by quickly enough and you'll have your test results and we'll be happy to chime in, share anecdotes and experiences and support you.

I remember how impatient I was too three summers ago. I can still feel that mix of incertitude that in the end I might not have ME/CFS and a gut feeling telling me that indeed that's what I had been suffering with and that finally I had found a doctor who tried to understand me and my condition.

@NK17 In some ways two weeks feels like an eternity and I am scared of what the results might show and just anxious to see them and get started. I left the appt very hopeful but with each passing day I start to have some doubts.

Part of me hoped he would say I did not have CFS but after spending two hours talking and examining me he said I was "One of the most classic cases he had seen" and met all the criteria. It was validating but made me very sad, too.
 

heapsreal

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@heapsreal thank you so much for all the info and I will definitely PM you once I am back home and when I get the test results.

My gut instinct is to start with Famvir both due to the cost and the potential side effects of Valcyte. I apologize for repeating this question but are both pill form (not injections, etc?)

Also, you mentioned that if someone is in the "right sub group" that the av's can really help which is basically what the specialist told me. Can you explain how it is determined what subgroup someone is in? Is it by which viruses you have?

For example (and I don't know yet in my case) but if someone has EBV and HHV-6 but not CMV is that a distinct subgroup?

Also which immune modulators did you take with Famvir? I got the sense that the specialist I saw does not do immune modulators but I could be wrong about this and need to check my notes which are in my suitcase. I think they can cause autoimmunity in some people?


Famvir is a tablet. Most docs won't know what an immune mod is. Most developed in Russia and other eastern Block countries. Although Dr's like Nancy klimas and other cfs gurus know about immunovir. Cycloferon do a search on here will get you plenty of info.

sub groups i guess u don't know until u start treatment and see how u respond. I guess the 3 main groups are ebv only, cmv and or have or a mixture of those. Plus there are some with other herpes viruses as well.

Ebv only should be able to do well on Famvir valtrex. Cmv/hhv6 groups can respond to Famvir but may need to add value. That's the easiest way to groupthem although theres nothing official . A good move is to try Famvir first and if need to move onto valcyte later? ?
 

NK17

Senior Member
Messages
592
@Gingergrrl43 I know it's difficult, but just try to think that now you've a specialist and he'll try to help you get better.

I know very well where you're right now, nobody in his right mind would want to have ME/CFS confirmed ...

Still you have to take the matter into your own hands, wait for the lab results and make a choice with your doctor. The choice will be based on the results as well as on your symptoms (what doctors call clinical history).

Some of us here on PR have gone or are going down the A/V road. I won't lie to you and tell you that it is easy and cheap, frequently it's not. Nor that it has a very high success rate.

Some drugs are milder and are considered a first line treatment (Famvir). Some are more 'hardcore', not in the sense that they are unjustified, but in that they have a reputation, a reputation that does seem, to the untrained eye of most doctors, to make sense if you want to suppress reactivation or new infection in post transplant patient or in HIV+ patients, but does not apply to us PWME.

That is one of the reasons why you went to seek Dr. Kaufman opinion and care. Because Dr. Kaufman is a trained doctor with a special understanding of our disease.

I'd like to remind you also that OMI was founded by Dr. Kogelnik and that he was a postgrad fellow of Dr. Montoya. Together they have done the very first clinical study with Valcyte on PWME/CFS. Both Dr. Montoya and Dr. Kogelnik continue to use Valcyte on the right subset of patients. I'm sure Dr. Kaufman is knowledgeable too.

You're in good hands. Nobody can promise you full remission, but your doctor will try his best to help you.

We're here to support your choices, we know that nothing is completely black or white, but we're pretty good at interpreting the many grey shades that make up our daily lives.

We're in this together, you're not alone.
 

Gingergrrl

Senior Member
Messages
16,171
@Gingergrrl43 I know it's difficult, but just try to think that now you've a specialist and he'll try to help you get better.

I know very well where you're right now, nobody in his right mind would want to have ME/CFS confirmed ...

Still you have to take the matter into your own hands, wait for the lab results and make a choice with your doctor. The choice will be based on the results as well as on your symptoms (what doctors call clinical history).

Some of us here on PR have gone or are going down the A/V road. I won't lie to you and tell you that it is easy and cheap, frequently it's not. Nor that it has a very high success rate.

Some drugs are milder and are considered a first line treatment (Famvir). Some are more 'hardcore', not in the sense that they are unjustified, but in that they have a reputation, a reputation that does seem, to the untrained eye of most doctors, to make sense if you want to suppress reactivation or new infection in post transplant patient or in HIV+ patients, but does not apply to us PWME.

That is one of the reasons why you went to seek Dr. Kaufman opinion and care. Because Dr. Kaufman is a trained doctor with a special understanding of our disease.

I'd like to remind you also that OMI was founded by Dr. Kogelnik and that he was a postgrad fellow of Dr. Montoya. Together they have done the very first clinical study with Valcyte on PWME/CFS. Both Dr. Montoya and Dr. Kogelnik continue to use Valcyte on the right subset of patients. I'm sure Dr. Kaufman is knowledgeable too.

You're in good hands. Nobody can promise you full remission, but your doctor will try his best to help you.

We're here to support your choices, we know that nothing is completely black or white, but we're pretty good at interpreting the many grey shades that make up our daily lives.

We're in this together, you're not alone.

@NK17 Thank you for reminding me that we are all in this together and I am not alone. I am not doubting my decision in any way and need to stop thinking of all the "what if" scenarios.

Dr. K told me that with anti-virals (assuming I turn out to have the viruses he suspects) that 1/3 make full improvement, 1/3 improve but once they stop a/v they go back to square one, and 1/3 do not improve.

Do you agree with those statistics?
 

NK17

Senior Member
Messages
592
@Gingergrrl43 I pretty much agree with Dr. K and I will also add that the sooner you find out the viruses and the sooner you'll intervene with the appropriate antiviral/s, the better.

Ideally we would also have a drug that regulates the immune system, but that is another story, for another thread/time ;).

I can tell you that if such a drug existed, Dr. Kogelnik would give it as candy (this are his own words), Dr. Kaufman would probably agree.
 
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