forced out of latency?? so what?

[mko]

I would like to ask everyone an open question:

several times over the last years, i came across the following words...

"the virus will be forced out of latency and then one can kill it..."

as you may have recognized, this is in reference to some "new" strategies that are currently being worked on by some "avant garde" researchers....for which i have the feeling you all made a lot of funding efforts!!

however, can anyone give me a very short and clear answer to this question"

"if the virus is forced out of latency.....and killed......what happens with the viral copies that are obviously SILL incorporated in our neuron's DNA?????"

so really, even if a treatment that forces the virus out of latency was one day created....that still wouldn't rid the neuron's nucleus of the viral DNA sequences that have incorporated themselves when infection took place the first time.

Latency is a state where this incorporated viral DNA does NOT express itself into viral proteins....making the virus "silent" during this so called latency.

"Blocking the latency" only means that you "prevent the virus from hiding"....but truly, this only means "preventing it from NOT-reproducting viral particles based on the Viral DNA incorporated in OUR nerve cell nuclei"

antivirals block this process, but have no effect on the virus DNA which is part for the neuron.

and forcing the virus out of it's hiding does't mean removing the virus DNA from the neuron either.

interfering RNA could block LATENCY, yes. but that just doesn't remove the virus DNA from the nerve cell's nucleus.

so i can't see that being a cure nor a treatment for a GH sufferer.

you all follow me?

[struggle83]

mko - I've been asking the same question for a while now. I don't know how activating can help. I think some theories involve keeping it permanently de-activated.

The only way I see activating might help is if the virus has been dormant for a while. When you activate it there are viral particles that are created and leave the infected cell. This leaves a trace of phosphatadyl serine on the surface of the infected cell. Drugs can be used to connect to these cells via the PS and can be used as markers for other drugs to come and re-activate the cellular apoptosis. This would eventually kill the infected neurons.

[SuperManFace]

When the HSV is latent, it doesn't stimulate the immune system. It doesn't cause a strong immunogenic response. So if it is out of latency forever, it will continue to stimulate the immune system, allowing the the HSV infected cells to be flagged and destroyed by the T-cells. When they are in latent mode, the HSV cannot be "seen" by the immune system. It gets far more complicated than that.

[SuperManFace]

mko - I've been asking the same question for a while now. I don't know how activating can help. I think some theories involve keeping it permanently de-activated.

The only way I see activating might help is if the virus has been dormant for a while. When you activate it there are viral particles that are created and leave the infected cell. This leaves a trace of phosphatadyl serine on the surface of the infected cell. Drugs can be used to connect to these cells via the PS and can be used as markers for other drugs to come and re-activate the cellular apoptosis. This would eventually kill the infected neurons.

Yeah your right. I remember this being the exact problem, the apoptosis process beginning, but one of the last stages halted through the mitochondrial pathways. It is basically cancer. The cells don't die.

[Movingslowly]

These scientist spend four years in undergrad, four years in medical school, then study their specialty. Last, but not least then gain experience from years of researching. Understanding this virus and how scientist will be able to cure people of the virus would take us just as many years as it did for them. Let's just continue to support a cure and hope that in another five years there will be breaking news for everyone who suffers from this horrible virus. May not seem soon enough, but remember for the first time ever in history has scientist believed they could cure people of this virus. I would be more than willing to go to the doc once a year and get an injection that 100% stops all shedding and outbreaks if this is all that ever comes from these researches. I highly believe a cure will come. The question is, when?

[SuperManFace]

These scientist spend four years in undergrad, four years in medical school, then study their specialty. Last, but not least then gain experience from years of researching. Understanding this virus and how scientist will be able to cure people of the virus would take us just as many years as it did for them. Let's just continue to support a cure and hope that in another five years there will be breaking news for everyone who suffers from this horrible virus. May not seem soon enough, but remember for the first time ever in history has scientist believed they could cure people of this virus. I would be more than willing to go to the doc once a year and get an injection that 100% stops all shedding and outbreaks if this is all that ever comes from these researches. I highly believe a cure will come. The question is, when?

You stay true to your name...

[death2herpes]

inhibiting the latency associated genes will just result in a perpetual megaoutbreak. will probably kill the host (directly or drive the host to commit suicide). not an improvement. if some 2ndary phase in a treatment plan involving targeting only neurons in active phase doesn't quite work 100% what then?

[SuperManFace]

Umm sir you have umm antibodies for umm herpes... You also have T-cells. Your T-cells is the reason your outbreak goes away. Then when it goes into latency your T-cells can't see it anymore. Also T-cells remain in the tissue at the initial outbreak site for several weeks after the outbreak. ANY virus you get infected with gets murdered within those two weeks it takes for your body to develop antibodies.. A virus has two-three weeks to infect you and cause disease. And even then it would get killed off, unless it has latency.

[death2herpes]

what's with the "umm"s? save your wise-ass sarcasm. you think every single infected neuron fires of virions during an outbreak? some percentage of them are active all the time, hence the asymptomatic shedding. infected neurons don't talk to each other, it is not an organized effort. what happens during a visible outbreak is that enough happen to become active to overwhelm the immune response. not all of them.

what do you think is going to happen when every single infected neuron is now sending a never-ending barrage of virions down the axons for the rest of your life? now replace the phrase "when it goes back into latency" in your post by "never" and think how your immune system is going to cope with a full perpetual outbreak.

there are some people who have outbreaks that last for 6 weeks. or sequential outbreaks back-to-back-to-back that don't get "murdered" by the T-cells. why do you think that happens? their immune systems and T-cells are not all-powerful and neither are yours. the reason the virus goes back into latency is bc... it decides to go back into latency, what is responsible for that is the latency associated transcripts, not your immune system pushing it back into latency.

why do you think the virus has evolved into this mild form that stays latent and asymptomatic most of the time instead of the simpler perpetually active form that it almost certainly previously was? the natural selection pressure is why this form prevailed, that's why. it was probably a very very nasty virus that was too harmful to the host.

but hey, you think it's a good idea to disable the LAT function of the virus and live with a massive perpetual outbreak, no problem. you can volunteer to be the guinea, good luck to you and your T-cells. umm.

[ATGC]

i dunno. sounds just so science fiction all this stuff. but during active infection you should be able to deplete the viral reservoir - and how? by resulting deaths of hosts? if someone gets back-and-back outbreaks shouldn't he be decreasing the pool then - and finally getting rid of it - if the virus is not let replenish the latent virus. that is simply the idea of forcing out of latency - if any. guess they know something these researchers-

[SuperManFace]

what's with the "umm"s? save your wise-ass sarcasm.

How about you save your face you sensitive little girl.

what do you think is going to happen when every single infected neuron is now sending a never-ending barrage of virions down the axons for the rest of your life? now replace the phrase "when it goes back into latency" in your post by "never" and think how your immune system is going to cope with a full perpetual outbreak.

Dude you take whole bunch of antivirals while while your LAT is disabled you shouldn't even have too many symptoms. How can you act like your so smart yet you forgot, or overlooked this little part, and didn't even bother to think about that.

why do you think the virus has evolved into this mild form that stays latent and asymptomatic most of the time instead of the simpler perpetually active form that it almost certainly previously was? the natural selection pressure is why this form prevailed, that's why. it was probably a very very nasty virus that was too harmful to the host.

Yes it did evolve like that, but it evolved to your immune system. So if your immune system is weakened you will have worse outbreaks. And if it is stronger you will have less symptoms. Meaning.....ummm sir..... YOUR GOD DAMN IMMUNE SYSTEM PLAYS A ROLE LOL!!!. It doesn't just go back into "hiding" because it wants to. If this wasn't true, people with severe immune deficiency wouldn't get ate alive by HSV, practically spreading everywhere, whole face and eyes and death and herpes in your fucking brain and so on.

[SuperManFace]

if someone gets back-and-back outbreaks shouldn't he be decreasing the pool then - and finally getting rid of it - if the virus is not let replenish the latent virus. that is simply the idea of forcing out of latency - if any. guess they know something these researchers

When you have back to back to back outbreaks some stay back in latency mode. Even then, it takes time to stimulate the immune system and clear the infection. So when your HSV is sleeping, and it wakes up, it has a specific window of opportunity for it to infect as many cells before your immune system gets hyped up and clears the infection, but the cells that were infected before the immune system was stimulated, go into latency. Besides like I said, some host cells won't release virions.

[ATGC]

I think my immune system is pretty much hyped up all the time and clears the the shit 24/7. And there is no latency at all. Killing killing killing. No mercy. (JUST GIVE ME THAT BAVITUXIMAB...)

[SuperManFace]

I think my immune system is pretty much hyped up all the time and clears the the shit 24/7. And there is no latency at all. Killing killing killing. No mercy. (JUST GIVE ME THAT BAVITUXIMAB...)

Damn, you think you have the wild type? In your case no doubt your body is killing HSV all the time, it just can't kill all of it the infection is too much. Not enough resources. They multiply more than your body can handle. If you had like 10² amount of T-cells I wonder if your body would be able to clear the infection.

[death2herpes]

How about you save your face you sensitive little girl.

save my face? i don't know what you are saying. i just responded to your uncalled for sarcasm with sarcasm (which was called for bc... it was a response).

Dude you take whole bunch of antivirals while while your LAT is disabled you shouldn't even have too many symptoms. How can you act like your so smart yet you forgot, or overlooked this little part, and didn't even bother to think about that.

eh, how do you know that? can you cite some studies conducted on subjects with LAT disabled HSV? no. again, only a fraction of latently infected cells go active during an outbreak. an even smaller fraction is active all the time. your contention that having all the latent cells go active, permanently, is no big deal and will make little difference in how your immune system + vatlrex is able to suppress it (which we know they generally cannot do completely even with LAT enabled) is totally illogical.

Yes it did evolve like that, but it evolved to your immune system. So if your immune system is weakened you will have worse outbreaks. And if it is stronger you will have less symptoms. Meaning.....ummm sir..... YOUR GOD DAMN IMMUNE SYSTEM PLAYS A ROLE LOL!!!.

can you please point to where i say your immune system plays no role? what are you talking about?

It doesn't just go back into "hiding" because it wants to. If this wasn't true, people with severe immune deficiency wouldn't get ate alive by HSV, practically spreading everywhere, whole face and eyes and death and herpes in your fucking brain and so on.

you are making my point. your immune system has limits. if it's sufficiently compromised it will not be able to handle even the small fraction of the latent pool that is active all the time. which causes disseminated outbreaks and eczema herpeticum and bacterial superinfections, etc. if the latent pool is sufficiently high even a healthy immune system will be unable to suppress all outbreaks, that is why we have them. this is with a virus that is primarily held dormant by the LAT.

let me make it really simple. LAT is a good thing, it is responsible for maintaining the HSV infected neurons in a state where your immune system can generally suppress it from causing excessive disease. yet *YOU* think turning it off is an improvement for some incomprehensible reason. and *I* think it will make it much worse for reasons that i think i have articulated about as clearly as possible at this point.

[SuperManFace]

Yeah man, but you were saying that the herpes goes latent because it wants to. You gave credit only to the herpes for why it goes latent. You didn't give any credit to the immune system clearing the infection, btw "clearing the infection" is medically used in science in regards to a local outbreak. By you saying "it decides to go back into latency, what is responsible for that is the latency associated transcripts, not your immune system pushing it back into latency." is in effect picking a side. This is like saying the immune system doesn't have anything to do with the infection being cleared which is what I was talking about. If what you said is true however, you said it in response to me talking about your immune system clearing some of the infection, so the context in which it was used can change the meaning because you saying "it decides to go back into latency, what is responsible for that is the latency associated transcripts, not your immune system pushing it back into latency." sounds more like a reason for something you believe that is in dispute with what I said when talking about the immune system clearing the infection. It is like basically saying it is only because of the LAT, that the cold sore goes away.

[Tiny]

I think it is great that the lovely scienticians are exploring all the options...I reckon they have years of training and a lot more understanding of microbiology than what we do. And I am sure a lot of mice and bunnies will give their lives before they ever take the risk of giving somebody some sort of "mega-constant herpes"....herpzilla...or The Incredible Hurp!

Personally on the brief summary of the theory that are currently available it does make sense in principal. And I'm not inclined to pooh-pooh any thing informed by years of research by people who are trained to do what they are doing. It may not work...but its like the lottery...you won't win unless you enter.

Personally I think the herpes developed the ability to go latent precisely so it could hide from your immune system and infect more people. I'm more inclined to believe that mutations was about viral self preservation rather than host preservation--but I inclined to give herpes as little power as possible.

That being said if somebody was going to switch on all my herpes at once...I'd like a nice little bit of morphine with that...or perhaps a restful coma for week or so.

[death2herpes]

Yeah man, but you were saying that the herpes goes latent because it wants to. You gave credit only to the herpes for why it goes latent. You didn't give any credit to the immune system clearing the infection, btw "clearing the infection" is medically used in science in regards to a local outbreak. By you saying "it decides to go back into latency, what is responsible for that is the latency associated transcripts, not your immune system pushing it back into latency." is in effect picking a side. This is like saying the immune system doesn't have anything to do with the infection being cleared which is what I was talking about. If what you said is true however, you said it in response to me talking about your immune system clearing some of the infection, so the context in which it was used can change the meaning because you saying "it decides to go back into latency, what is responsible for that is the latency associated transcripts, not your immune system pushing it back into latency." sounds more like a reason for something you believe that is in dispute with what I said when talking about the immune system clearing the infection. It is like basically saying it is only because of the LAT, that the cold sore goes away.

you don't understand. although latency is not fully understood at molecular level it is known that during latent phase there are no detectable lytic HSV transcripts, only LAT. unfortunately it is not understood exactly how latency is established during intial infection.

but that is the key to understanding why there is a reversal and the silent genomes are re-expressed during reactivation, and again silenced. reactivation/latency is a process that is controlled by some HSV mechanism, NOT commanded by the immune system bc this is going on inside the HSV-infected neurons where the immune system does not go.

yes, the immune system does clear the "cold sore", that is just virions that have been sent down the axon to the epidermal cells, they will continue to multiply and disseminate after the reactivation at the neuron level is finished unless the immune system supervenes. that is actually the sore, it is the immune system destroying the infected epidermal cells, not HSV.

so i repeat. disabling latency is a very dangerous thing to do. having the entire latent pool reactivate will cause a monstrous outbreak. even if it is a 1-time outbreak, it is not clear how your immune system will be able to handle it. i repeat, the percentage of latent reservoir that goes active during a normal reactivation is very small. look here http://www.ncbi.nlm.nih.gov/books/NBK47421/

"A further serious complication arises from the fact that reactivation is an inefficient process with only a small proportion of the neurons that harbor viral genomes responding by production of virus."

furthermore, the outbreak will be neverending UNLESS those active neurons are seen by your immune system (or some drug that does not yet exist) and destroyed.

[Tiny]

furthermore, the outbreak will be neverending UNLESS those active neurons are seen by your immune system (or some drug that does not yet exist) and destroyed.

I really don't think that what they are proposing is killing your "infected" neurons. They are talking about a virus that lives in your body alongside your actual cells the ones that as a group are referred to nerve bundles, neurons ect.

Valtrex does exist, and that is the drug they are talking about using.

Valtrex (at least the way I understand it) disrupts the herpes ability to reproduce giving your immune system less virus to fight.

It is a treatment that would work now to completely eradicate the herpes virus, if herpes wasn't able to disguise itself and hide in your body alongside your cells. What they are investigating is taking away the herpes ability to hide...then using drugs to supplement your immune system and get rid of it completely.

I doubt they would be pursuing this course of study, entering phased trailing and publishing papers if they didn't have pretty good science backing it up. People have their professional reputations and a lot of money on the line—and those are pretty effective motivators.

death2herpes: As my dr says…leave the science to the experts. The fact is there is a lot about this research that will not be published now as research is a highly competitive arena—it really is not something that is done out of a sense of altruism…people do it for money and prestige. Having your research stolen and realised by somebody else before you is a very real risk so what is published is teaser to wet people appetites (and get investors) but not enough to allow anybody else to pip them to the post. There really is no point in arguing that it will not work...because you are probably not directly involved in the research and therefore simply do not have all the information available. Sure it doesn’t make sense to you…and you can’t see how it might work and think it might be dangerous…and that is fine…but there are a lot of people who really need the hope, who need to know that there are people out there working on this. If it doesn’t work or fails in Phase 1 it will never become available…no harm done (unless you are maybe a rabbit or something)…if it does and you still don’t trust the science then you don’t have to take it. It is not worth making other people afraid and taking away their hope…when you just don’t know for sure.

It’s the herpes cure lottery…got to be in it to win it!

[mko]

I m afraid you guys all don't quite understand much about viruses.

They all work differently. You can't compare them just because they are all called viruses.

And latency is by far not even the only think that makes them different.

If you just take HSV 1 and 2 for example, dont be fooled by the fact they are both herpes, both called HSV and have common genes and have similar clinical signs and simptoms....they are very different!!!!

next, please, define in one or 2 lines, what do you call "kill" and what do you call "clear" HSV2

also define how Valtrex is supposed to do the job. Actually use Aciclovir, because that is the molecule we talk about.

for reminder, Valacyclovir is transformed into aciclovir by your liver during first pass.

If you dont all define your words, you ll always end up fighting.

And we wont learn much from each-other.

Mko

[struggle83]

I m afraid you guys all don't quite understand much about viruses.

They all work differently. You can't compare them just because they are all called viruses.

And latency is by far not even the only think that makes them different.

If you just take HSV 1 and 2 for example, dont be fooled by the fact they are both herpes, both called HSV and have common genes and have similar clinical signs and simptoms....they are very different!!!!

next, please, define in one or 2 lines, what do you call "kill" and what do you call "clear" HSV2

also define how Valtrex is supposed to do the job. Actually use Aciclovir, because that is the molecule we talk about.

for reminder, Valacyclovir is transformed into aciclovir by your liver during first pass.

If you dont all define your words, you ll always end up fighting.

And we wont learn much from each-other.

Mko

There are many similarities to viruses. That's why an anti-viral medicine can be effective across a range of viruses. For example, Ribavirin has a broad spectrum of viruses. Viruses all have a life cycle and they are fairly similar. We shouldn't worry about differences when formulating medicines, only similarities.

Personally, if I was going to take something that brought the entire viral pool into activity I would have pre-treated myself with antivirals like Ribavirin and CMX001. I would expect that already having highly effective antivirals in my system would thwart a possible neural-viral catastrophe.

[mko]

ok struggle83

Just one question, do you have any educational background in molecular biology, genetics, medicine?

I m afraid you have miss-interpreted a lot of things that are written on the subject.

You may nevertheless enjoy reading about it.

But I feel it may be best to start with some very basic concepts such as:

transcription

translation

histones, chromatin, dna

rna

polymerase, nuclease, helicase

axonal transport

The best is read this from a basic premed book, you may find this in any larger bookshop.

Then, you may look more specifically into hsv by jumping directly into the dna viruses.

But you may prior to that learn about immunology.

This part may be a little more difficult to understand.

Because I think you are incredibly over simplifying things and you don't realize that certain things that you write make no sense at all.

I do not mean to offend you in any way.

I appreciate the complexity of the matter and things are overly complex.

There are so many aspects to integrate making it impossible to explain the "why" in simple words without ending up writing a textbook.

You must in the end understand this:

DNA viruses incorporate their genetic material into the DNA strand of the target cell of its host.

(here the neurons of the afferent sensory nerves) via retrograde axonal transport.

Once incorporated into the host DNA, its part of it....that means it is just information within the normal DNA.

You have to understand that is it literally incorporated in it. There is no scar left on the DNA, it's purely information.

This viral DNA information is TRANSCRIBED into RNA along with the rest of the host DNA it is entirely part of.

So the RNA produced is the normal and the viral one.

Now read this carefully:

The antiviral aciclovir or ANY OTHER antiviral just SLOWS (it can never BLOC ALL) the Polymerases or other enzymes involved in the TRANSCRIPTION of DNA into RNA.

It cannot bloc all because there is competition between the normal nucleosides and the aciclovir, or any other enzyme blocking molecules.

To understand that concept you need to read the chapter about competitive, un and non competitive pharmaco kinetics. Don't even believe you understand about antiviral treatments without mastering this basis of biochemistry.

Now you may be able to understand that the end result will only be to slow the production of RNA including the viral one.

You can never remove the source: the incorporated viral DNA.

Now, next step for you is to understand that latency, that's just again a pharmacokinetic concept.

The virus never sleeps.

People just say it goes to sleep so that the general public has sort of a concept in their minds.

But that is incorrect infact.

The only thing that changes in the kinetics. the rate of TRANSCRIPTION.

So forcing out of latency, you just increase the RATE.

Nothing more.

Last, dont forget one thing.

Everytime you have a viral particle produced by your Infected neuron.....it sends viral particles along the axon to the skin.

And there, just a question of rate, but you have new viral particles going back the other way, RE infecting the same NEURON and OTHER neurons.

That way, you always have a guarantee that you always have fresh new copies of viral dna in your dna.

and you may even develop is somewhere it wasn't before.

And the virus doesn't actually need to have the lesion coming to the skin surface, it can just jump within the tissue to neighbouring nerves and neurons.

For example, we have patients with a perfectly normal immune system where the virus spreads to the brain.

And I 'd appreciate that you dont tell me the HSV 1 and 2 are the same.

They are not, they have very different kinetics, and even weapons, that can cause death or not according to what they infect.

anyway, this was just a little introduction.

you have the list of subjects you need to read about above.

expect to read so several weeks before you even begin to truly understand the subject.

just to know what you are reading about is not enough.

and understanding means being able to argument and criticize a scientific paper on the matter.

and i m not talking about you making some philosophical statements.

happy readings to you.

If you have questions, you may ask them, but be precise, use short sentences and accurate words.

The original title of the thread remains, forced out of latency, so what.

I still wait for a sound argumentation about how this can help.

Regards

Mko

[death2herpes]

that is my point, it will clearly make it worse. however, there is the below highlighted comment in the conclusion to the article i posted the link to:

"Latency is clearly very complex at the molecular level, and the difficulties inherent in the model systems ensure that it will not be unraveled easily. The non-uniformity of latency, in terms of viral genome copy number, LAT expression and nature of reactivation stimulus, may be of fundamental benefit to the virus. If latency was uniform, a single stimulus might induce reactivation in the entire latent reservoir and result in clearance of the virus from the host. Perhaps the different virus/cell interactions respond to different host signals, explaining why it has been so difficult to arrive at a simple model for the molecular basis of latency."

this comment i do not understand. this is not my area of expertise, if someone understands this, please weigh in.

[Tiny]

mko: thanks for the info.

I have absolutely no background and understanding of science, but I do have one in psychology. And I believe that for the majority of people understanding their bodies and viruses in simple terms is enough. I only added to this thread as I feel that having herpes causes enough paranoia and knowing that people who do understand virus are pursuing this course of action and consider it promising is what is important. I apologies for offering an overly simplified view or if I said anything silly. I certainly felt some of the things death2herpes and you were saying made me feel powerless and anxious…like there was no hope…and we should all just give up now…or tear every “infected” cell from our bodies…and I imagined others might have felt like that too. Yes there is information (which is by no means exhaustive) and it is being read and interpreted by lay people who really want to have a “normal” herpes free life.

I think the reality is that most people on here are sufferers (I hate that word) or people who in some way are affected by herpes not scientists or drs. Therefore the arguments that you are going to get are from people (maybe a little bit blinded by hope) who want to live in an ideal world where this will work (and are trying to rationalise that it will—because they need to do that psychologically to cope in their everyday lives…we are looking for a light at the end of the tunnel). You may find it ignorant, self-delusional or naturally frustrating…but honestly you are probably not picking the right people to debate with. If you want real arguments, answers or discussions seek out people who do have a medical or virological background—I’m sure it will be much more fulfilling for you and you will probably get responses you can respect.

[death2herpes]

death2herpes: As my dr says…leave the science to the experts. The fact is there is a lot about this research that will not be published now as research is a highly competitive arena—it really is not something that is done out of a sense of altruism…people do it for money and prestige. Having your research stolen and realised by somebody else before you is a very real risk so what is published is teaser to wet people appetites (and get investors) but not enough to allow anybody else to pip them to the post. There really is no point in arguing that it will not work...because you are probably not directly involved in the research and therefore simply do not have all the information available. Sure it doesn’t make sense to you…and you can’t see how it might work and think it might be dangerous…and that is fine…but there are a lot of people who really need the hope, who need to know that there are people out there working on this. If it doesn’t work or fails in Phase 1 it will never become available…no harm done (unless you are maybe a rabbit or something)…if it does and you still don’t trust the science then you don’t have to take it. It is not worth making other people afraid and taking away their hope…when you just don’t know for sure.

It’s the herpes cure lottery…got to be in it to win it!

the point of discussing things is to inform each other so we can understand how what may work and distinguish the potential benefits / risks of different ideas. if you just say to yourself, well we have inadequate background in this field or inadequate information due to some secrecy to understand anything anyway, then there is no point discussing anything in this section is there?

there are different ideas out there and some will have better potential than others. you care which ones, don't you? i do not see how bringing the entire reservoir permanently out of latency is useful. so i question the utility of this approach. and i do not need to apologize for that. if someone can offer a viable explanation i would love to hear it. but there is no benefit for someone who doesn't understand even the terms to disseminate misinformation and argue over trivial facts.

your "immune system" does not target HSV-infected neurons. and valtrex has nothing to do with this. it only partially inhibits viral replication. and there is no drug out there that will target the affected neurons either. except maybe bavituximab if it works, but if it does that's all you will need anyway. so, what's the point of disabling latency?

Now, next step for you is to understand that latency, that's just again a pharmacokinetic concept.

The virus never sleeps.

People just say it goes to sleep so that the general public has sort of a concept in their minds.

But that is incorrect infact.

The only thing that changes in the kinetics. the rate of TRANSCRIPTION.

So forcing out of latency, you just increase the RATE.

Nothing more.

i disagree with that somewhat. yes, the difference is the rate. but the rate of transcription is actually zero, all viral genes are silenced during latent phase. that's why bloom's reverse approach sounds promising, to render HSV-infected neurons unable to reactivate.

people say "it" goes to sleep which is incorrect for entire latent pool since there are many infected neurons and latency is non-uniform mechanism so they are never "all" asleep. but if you are talking about a particular neuronal nucleus, there is no viral genome expression during latent phase except for LAT. as far as we know. anyway, that is my understanding from what i have read...