HIV Think Tank

[Sayonara]

HIV is a serious threat to present and future generations, as you will know if you follow the news and science papers. It would be interesting if we could maintain a 'Think Tank' to collate current approaches to fighting the virus, and to process the plausability of conjectural treatment.

 

It has occurred to me recently that where there has been much research into the prevention of T4 - HIV interactions through inhibitors etc, there does not seem to be any research that exploits the virus' affinity for this structure.

 

So, some questions:

 

 

• Red blood cells have a far greater volume than T4-lymphocytes, no nucleus, and are more numerous by a long way. Would blood oxygen carriage suffer if they expressed T4 receptors on their membranes, and carried a payload of inert viral genetic material?
  
• If 'yes' - how severe would the effects be?
  
• If 'no' - then...
  
• Is it possible to apply gene therapy to stimulate expression of T4 on the surface of erythrocytes?
  
• If 'no' - Oh well.
  
• If 'yes' - would HIV be completely 'mopped up', or would it persist in low-medium yields?
  

 

Discuss, expand and find linkage!

 

[fafalone]

Actually there is an immunology forum... moved

[Sayonara]

Damn my squinty CRT eyes.

 

Ta

[fafalone]

Erythrocytes are hemoglobin based, and the structure has 4 binding sites sticking out for oxygen, so if there was something blocking those sites oxygen carrying would be signficantly impaired. Even if they were genetically engineered to have properties of T4's, it wouldn't be a great idea since introduced a virus to "infect" erythrocytes, it would increase the viral load and trigger an immune response. That's the primary problem with gene therapy today. Their effect on HIV is questionable, because I haven't heard of in vitro studies that suggest they could stop HIV if there were simply more of them. If this were the case, I suspect we could produce mass quantities of these cells in vitro and introduce them to the affected subject in vivo.

[Sayonara]

Originally posted by fafalone

Even if they were genetically engineered to have properties of T4's, it wouldn't be a great idea since introduced a virus to "infect" erythrocytes, it would increase the viral load and trigger an immune response.

 

Do you mean that superpresence of T4 would incite increased immune activity, or that viral material in erythrocytes would?

 

If the latter, I would expect that viral material injected into a red blood cell would be sequestered and therefore (a) not detected by the immune system, and (b) completely biologically useless due to the lack of a nucleus in the blood cell.

[fafalone]

That raises an interesting oversight, I do not believe erythrocytes are actively involved in protein production, therefore couldn't be engineered to produce anything. The virus would have target erythroblasts, the immediate nucleated precursor to erythrocytes. The body wouldn't know the invading virus was helping instead of harming, so there would be an immune response to the virus itself.

[Sayonara]

The idea here is for the virus to discharge its genetic material somewhere where it will not be able to replicate - the use of a red blood cell as a decoy target is the optimum approach as they have such a massive presence in the body. However, it could just as easily be any cell that will not duplicate viral RNA. It might even be fat deposits.

 

Since RBCs have no active protein processes, it would be necessary to specify T4 production during the cells' development in the bone marrow (which would of course be a feat, but then this is all conjectural.)

 

Could you please elaborate on the viral target erythroblast problem, as I suspect this may be pivotally relevant.

[fafalone]

Well in order to change the structure of erythrocytes and platelets, you'd have to change the type of cells that peform erythropoiesis and thrombopoiesis (erythroblast and megakaryocyte, repectively). The challenge lies in having a virus deliver its DNA or RNA without provoking a cell response that normally happens when a virus enters a cell. Since viruses cannot differentiate one type of cell from another, it infects all cells. This generally creates an immune response where the system will destroy the infected cell. People who undergo genetic therapy are normally given immunosurpressant drugs... but I don't think that's a good idea with an HIV infected person.

[Sayonara]

Since an erythrocyte does not carry out protein synthesis processes, would it not be the case that an infected RBC would fail to get 'flagged' as infected?

[fafalone]

Most viruses don't affect erythrocytes, but all the cells above it would be effected... and the life span of an erythrocyte is only 120 days, so in turn it would cause a depletion of available RBCs and oxygen deprevation.

[Sayonara]

Yes, the short RBC lifespan is a double edged sword - we get rid of massive amounts of viral RNA that would otherwise have been used to infect active cells, but we are forced to use a method for permanent replacement of the T4\RBCs.

 

It's pretty obvious that this approach will not stop the virus (at least, not very quickly), but if it could be made to work it might slow down the spread of infection to a remarkable degree. Let's review what we have so far:

 

Advantages:

• RBCs expressing T4 could act as decoy targets for HIV
• RBCs have no nucleus and therefore cannot duplicate viral RNA
• Infected T4\RBC destroyed in liver after about 3 months, taking sequestered viral RNA with it
• RBCs are extrmely numerous in the body and are transported through most tissue groups - effective exposure of the virus to T4\RBCs will be phenomenal

Problems:

• Expression of T4 itself may reduce oxygen transport into and out of RBC
• Effects of viral RNA held within a T4\RBC difficult to predict
• Erythropoiesis and thrombopoiesis processes must be modified in a way that results in permanent T4\RBC production (although not all RBCs need express T4)
• Viral target erythroblasts may be a problem

Other factors:

• Immunosupressance due to the action of HIV may actually help the therapy progress without triggering a large immune response

Offshoot Concept:

• Non-nucleated cells expressing T4 receptors could be produced in vitro, and introduced to the patient in order to act as 'mouse traps' for the HIV virus. Such entities would require a tissue match with the patient - the easiest way would be to clone them from the patient's own tissue.

[Sayonara]

Since this is a Think Tank thread, I suggest we depart from the usual point/counterpoint flow of discussion and take a modular approach.

 

Let me explain...

 

Say we start with a basic outline for an idea (such as, ooh, decoy RBCs). If a part of it is problmatic or just won't work, we snip it out and replace it with something that will.

 

Hopefully this approach will mimic selection processes, and the idea will evolve towards something that is both workable and practical.

[fafalone]

We all wish we knew something that would actually work :/

 

BTW has anyone heard of any results from the vaccine tests they're doing in Africa for the past couple of years?

[Sayonara]

Originally posted by fafalone

We all wish we knew something that would actually work :/

 

BTW has anyone heard of any results from the vaccine tests they're doing in Africa for the past couple of years?

 

Of course we do - but if you're not familiar with Think Tanks the idea is that everyone brings something unique. Not everyone can have all the pieces of the puzzle. With a problem like HIV to work on, it's at least worth a shot.

 

Not heard anything about the vaccine trials yet, sorry. Asked Google yet?

 

 

Righto, I'm off to get mildly drunk in celebration of my late start at work tomorrow...

[John]

I remember watching a television program about HIV and AIDS, which mentioned prostitutes in Africa who were apparently immune to HIV. The show had a wonderful 3D rendered sci-fi representation of the human body as a futuristic city, with all sorts of things traveling through, but that's unimportant here. I found an article online which briefly describes a similar trend:

 

http://www.aegis.com/news/newsday/1998/ND980701.html

[Kylon]

Some areas you might want to look into future possible cures are-

 

Prions which would be highly unpredictable but, perhaps we could make a prion that would convert the HIV virus to it.

 

Like Mad Cow disease, if we took some prions that were growing, destroying, ect... ect... and introduced tons of different types of proteins, and alot of HIV, then I am thinking that the prions mutating all the other proteins in the process may eventually find a protein type that would effectively convert HIV to Mush.

 

This is probably far more dangerous than the other ideas but its fun to think about!

 

Also, I was thinking of something similar to the decoy blood cells, instead of red blood cells, dead cancerous white blood cells.

 

Advantages are, there is very little tricky genetic engineering. If by chance, the virus mutated and attached itself to the other receptor then it would still kill the virus, HIV would not just be temporarily trapped, since it would be dead it would be passed out of the system rather quickly. Blood poisoning is a prob though

 

Also, this has more than likely been thought of, and I am probably wrong, but...

 

They have tricked the body into thinking that niactin is bad for it(it is but it doesn't usually trigger an immune response) If they were to kill HIV, and use similar techniques to trigger a immune response, they might be able to make a vaccine. Cuz HIV usually kills the cells that make anti-bodies right?

 

Sorry about grammar and spelling. Time is scarce and I have long messages.

[Guest DeeTee]

I don't know if setting up decoy cells for HIV binding would work in practice.

 

Certainly about 5 years ago there were trials of "soluble CD4 receptors" wherebye the patients were given infusions IV or SC injections of the relevant binding receptor. These did not need to be bioengineered into RBCs or another carrier, you just had millions of them floating free in the plasma to gum up all the GP120 sites on the virus.

 

It didn't work, but I am not sure if anyone has looked again more recently at what was a good theory.

[Hades]

the problem with HIV is the body can not recognize its being attacked. My idea was to synthetically produce the chemical that would trigger our immune system to begin making antibodies. The only other question, would these antibodies destroy the virus? Antibodies destroy other viruses, would this retrovirus be unique?

[MishMish]

I thought the problem with HIV was the high mutation rate

[Hades]

theres many aspects of the disease that hinder our ability to produce either a cure or preventitice medicine. The mutation rate is also one of them, but what would happen if we were able to release antibodies to destory the virus?

[MishMish]

Afraid I don't understand your question

[psi20]

Would the human immunodeficiency virus attack non-human animals?

 

Has there been reports of animals having the HIV?

 

If not, then what would happen if you put the virus into the animal's system?

[YT2095]

recent news heard this morning on Sky News, the American porn industry is on a 2 month hold, as 2 "actors" have been found with AIDs, it started with this one guy who had unprotected sex with 13 other women one of whom caught it. now there is quite some alarm and they have all agreed to wait 2 months and have everyone tested again.

it`s feared that some smaller companies might not bother and carry on regardless

[Dave]

It just shows that no matter how many precautions you take (and I presume they take quite a few), you can't always stop this thing. Of course some of the small companies are not going to bother; potentially it's a lot more profit for them.

[Sayonara]

Arrrrgghhhhhhh you don't 'catch' AIDS.

 

It's a syndrome which may result from being infected with an immunodeficiency virus.