EBV Latency

[Daffodil]

for those of us who got CFS after EBV......i was reading about "chronic EBV infection" and came across some articles saying that Hydroxyurea can induce the lytic cycle of EBV. They use it some some EBV-induced cancers cuz antivirals do not work on those...they are caused by the EBV Latent Membrane Proteins.

Lets say our disease is also similar to an EBV-like cancer and the latent proteins are to blame.....what if we were to take hydroxyurea WITH some antivirals? Maybe that would cause eradication or near-eradication of latent EBV by activating the latent EBV and letting the antivirals kill it off...?

They eradicated EBV in a cell liine with hydroxyurea here:

http://www.ncbi.nlm.nih.gov/pubmed/9593003

I also came across an article about a man in Germany who went to see a doc after very recently being infected with HIV (he had a "flu"). The doc gave him HAART + Hydroxyurea (ha! the Germans will do anything). I guess he must have had a very low latent reservoir at that point, because 5 weeks later, he stopped all meds and remained in remission.

They give people with sickle cell anemia Hydroxyurea so maybe it is doable???

There is also Gemcitabine which induces lytic cycle.....cuz EBV can become resistant to Hydroxyurea.

 

[alex3619]

I would be very very careful about inducing a lytic cycle in CFS patients. I would like to see proper studies and clinical trials first, I think it might be very dangerous for us. In addition I think our whole notion of viral lifecycles might be inadequate. They are for enteroviruses which appear to have two extra lifecycles and I suspect this might also apply to herpes viruses due to Lerner's findings of viral particles and antibodies to the interior of the virus.

I am worried about lytic cycles because if any of the tissue load is replication competent, and I am not sure much of it is, then it could destroy the integrity of that tissue. Inducing the lytic cycle is only useful if you presume a low viral tissue load. In us I do not think this is the case.

 

[Daffodil]

ur right! plus God knows which other viruses it might induce

guess i gotta stick with gcmaf

 

[August59]

Who knows we may be stuck in a chronically activated lytic cycle anyway. We by no means follow at typical EBV cycle and an overacive lytic cycle could be why our antibodies for EBV ae running so high. It's just a thought because it seems obvious to me that there is something wrong with, at least a portion of us, with the way our bodies are not able to hold down the re-activating of the EBV.

This could be the reason the rituximab studies are no going well when people with CFS stop taking the rituximab and stop and return to being very ill within a few weeks. It would seem that it has something to do with the body building up it's supply of B-cells and if all these B-cells are provoking EBV into re-infecting them then you are going to feel like $hit, I would think.

This would be a great thing to study after the rituximab studys (if they ever get started). I hope they do'nt just stop with the rituximab. If their are some to relapse this would be the perfect time to study anything they possibly can because there is almost a guaranteed shot of being able to study someone that is in a major phase of CFS and I would haate to see this moment wasted. Could be malformed B-cells, malformed antibodies or a polymorphism that is getting activated, but how you would tell this I'm not sure. A mass activation of Mast(?) cells. Who knows????

 

[alex3619]

Hi August 59, the two alternate entervirus lifecycles translate to a slow release of both fully formed viral particles and partially formed virus particles. Its a trickle feed, not a storm like the classic model of viral infection. What does this mean for the immune system? Nobody knows for sure, but my current best guess is it means ME. This has not really been investigated. As far as I am currently aware, despite some evidence from Lerner's research, its not known if this is also correct for herpes viruses. I will be looking into this soon.

Rather than induce classic lysis, I suspect (and this is my interpretation) that the cells will be compromised with a high viral load, but those viruses will only be released when the cell dies by more normal means. One of the two lifecycles fits this pattern, though the other I am less sure of. I am going to have to further investigate the entervirus literature.

The other problem is there is a risk, but I do not know if this is well established, that these viruses can infect adjacent tissue without alerting the immune system. We really really really need more research on this.

Bye, Alex

 

[Daffodil]

well the thing is that my antibodies were never high other than when i had the acute infection 20 yrs ago. and in the chronic EBV papers, they state that antibodies are not high in everyone. they also state that there is a difference in the EBV that becomes chronic...i am trying to find where i read this. something about polyclonal vs monoclonal....

i am not sure what the hydroxyurea does with the EBV....in HIV it inhibits DNA synthesis or something.....but it does something to the EBV too...and helps remove the latent reservoir of EBV somehow - in the cell lines they studied.

i am wondering why the low dose hydroxyurea they give to sickle cell anemia patients, long term (i think) doesnt induce their viruses to start lytic cycle...i mean that would be harmful..?

honestly i do not understand the merit of the rituximab studies. isn't it a given that the remission with rituximab will last only a few months at best? sorry i dont know much about this but this is what i keep hearing.

anyway, if its the latent membrane proteins of EBV causing the problem, the lipkin pathogen study should find them...i hope :-/...as long as they are sufficiently similar to the proteins they know about already. i doubt it is some drastically different EBV strain

 

[heapsreal]

well the thing is that my antibodies were never high other than when i had the acute infection 20 yrs ago. and in the chronic EBV papers, they state that antibodies are not high in everyone. they also state that there is a difference in the EBV that becomes chronic...i am trying to find where i read this. something about polyclonal vs monoclonal....

i am not sure what the hydroxyurea does with the EBV....in HIV it inhibits DNA synthesis or something.....but it does something to the EBV too...and helps remove the latent reservoir of EBV somehow - in the cell lines they studied.

i am wondering why the low dose hydroxyurea they give to sickle cell anemia patients, long term (i think) doesnt induce their viruses to start lytic cycle...i mean that would be harmful..?

honestly i do not understand the merit of the rituximab studies. isn't it a given that the remission with rituximab will last only a few months at best? sorry i dont know much about this but this is what i keep hearing.

anyway, if its the latent membrane proteins of EBV causing the problem, the lipkin pathogen study should find them...i hope :-/...as long as they are sufficiently similar to the proteins they know about already. i doubt it is some drastically different EBV strain

isnt kogelnik doing or going to do a study with ritux and valcyte, maybe this could put someone into remission alot longer then ritux alone?

 

[Daffodil]

hi heap. i would think that for long term remission, one would have to get rid of ALL B cells....does rituximab get rid of all of them?

 

[heapsreal]

hi heap. i would think that for long term remission, one would have to get rid of ALL B cells....does rituximab get rid of all of them?

Dont know but maybe with ritux and antivirals this can be done. Av's could maybe stop new b-bells getting infected.
Be interesting if/when a study gets done on it??

 

[Daffodil]

hi heap

i am not sure if AV's will stop new cells from being infected...if the virus is just pumping out latent proteins, i think its resistant to AV's....not sure. AV's dont work in EBV-associated cancers...

 

[heapsreal]

hi heap

i am not sure if AV's will stop new cells from being infected...if the virus is just pumping out latent proteins, i think its resistant to AV's....not sure. AV's dont work in EBV-associated cancers...

Its hard to know?? they arent always right, its not even accepted that ebv reactivates in us, even though we know it does. I suppose av's and maybe ritux is all we have at the moment and all we can throw at it for now??

 

[Daffodil]

well....B cell depletion and AV's together doesnt work on EBV associated cancers but there is a new drug they are studying that blocks EBVNA1 protein...a latent protein. its called Hsp90 inhibitor:

http://www.med.wisc.edu/news-events...ral-epstein-barr-virus-induced-diseases/26288

 

[Daffodil]

and

http://www.hsp90central.com/auy-922.html

 

[alex3619]

well....B cell depletion and AV's together doesnt work on EBV associated cancers but there is a new drug they are studying that blocks EBVNA1 protein...a latent protein. its called Hsp90 inhibitor:

http://www.med.wisc.edu/news-events...ral-epstein-barr-virus-induced-diseases/26288

Wow Daffodil, nice find!

 

[Daffodil]

thanks alex. this was discussed in another thread months ago:

http://forums.phoenixrising.me/inde...shut-down-several-ebv-induced-diseases.18673/

 

[Daffodil]

heat shock protein 90 new developments:

http://www.medchem.ku.edu/faculty_blagg.shtml

 

[frederic83]

Reactivating the lytic cycle of EBV and antivirals seems to be a good strategy, Here is a new one, genipin.

That is the strategy they follow with EBV-induced cancer.

But I don't know if it works on non-cancerous cells. I think a reactivating chemical of the EBV on normal cells is what we are looking for.

 

[Biarritz13]

for those of us who got CFS after EBV......i was reading about "chronic EBV infection" and came across some articles saying that Hydroxyurea can induce the lytic cycle of EBV. They use it some some EBV-induced cancers cuz antivirals do not work on those...they are caused by the EBV Latent Membrane Proteins.

Lets say our disease is also similar to an EBV-like cancer and the latent proteins are to blame.....what if we were to take hydroxyurea WITH some antivirals? Maybe that would cause eradication or near-eradication of latent EBV by activating the latent EBV and letting the antivirals kill it off...?
.

"The majority of the world’s population becomes infected with multiple herpesviruses during childhood, and after clearance of acute infection, viral latency is established in the host and persists for life [104,105]. On one hand, latency is deemed a beneficial symbiotic relationship, but to this notion’s detriment, it is also noted that viral persistence in latent phase is the greatest obstacle for effective antiviral therapy [105,106]."

Latent phase is an obstacle to antiviral, maybe not to lytic which can be induced with genipin.

 

[Daffodil]

how interesting, thanks @Theodore

 

[Justin30]

"The majority of the world’s population becomes infected with multiple herpesviruses during childhood, and after clearance of acute infection, viral latency is established in the host and persists for life [104,105]. On one hand, latency is deemed a beneficial symbiotic relationship, but to this notion’s detriment, it is also noted that viral persistence in latent phase is the greatest obstacle for effective antiviral therapy [105,106]."

Latent phase is an obstacle to antiviral, maybe not to lytic which can be induced with genipin.

Vaccine for Herpes Viruses?