I have been reading up on the Herpes Simplex Virus and became curious as to why no cure has ever been developed. The best explanation I could find was:
"Herpes simplex virus (HSV) infects epithelial cells (skin cells) and
replicate in them quite rapidly but the immune system fights off the
infection in about two weeks because the replication is high and that HSV
does not “hide” in skin cells. During the first infection, however, some
viruses also infect sensitive nerves near the site of infection and are
transported along the axons to the neuron itself where it enters a latent
stage. During this time, the virus’ DNA is circular and the virus does not
express any of its proteins, which makes it “invisible” to the immune
system.
Following reactivation of the latent virus after, for example, exposure to
cold, UV light, stress, or if the patient becomes immunocompromised, the
virus migrate again towards the epithelium along the axons to infect
epithelial cells and cause lesions."
-Why is herpes incurable? - Answers
So it is my understanding - and please correct me if I’m wrong; the reason there is no cure is because the virus is able to hide from the body’s immune system by not expressing any of its proteins during its latent stage.
My question is instead of trying to develop medicines or cures to beat the virus, would it be at all viable to either:
tack a protein strand on to the virus so the body could recognize it and destroy it,
or induce something to the body that would aggrivate/activate the virus long enough for the body to take care of it?
As my background is not in medicine I would like to hear from anyone who could enlighten a curious individual.
During this latent phase, the virus is present as a piece of DNA within a nerve cell. Normally, cells infected by viruses present viral antigens (peptides derived from viral protein) on the cell surface. These allow T-cells to recognize cells infected by viruses, and kill those cells. Nerve cells do not express the class I MHC molecules needed to display the viral antigens. Therefore viruses hidden in nerve cells are hidden from the immune system.
(Neurons, unlike glia and most other cell types, fail to express major histocompatibility complex (MHC) molecules, even in response to IFNγ. Journal of Neuroimmunology
Volume 123, Issues 1–2, February 2002, Pages 35–40)
The problem is that nerve cells serve as a reservoir for the virus. Even if you could attach a marker of some sort that would allow the immune system to attack the virus where it survives in latent stage, that would mean coaching the immune system to attack nerve cells. Nerve cells don’t regenerate like epithelial cells or other tissues, so in destroying virus infected cells, you would permanently damage nerves.
The neuralgia that often accompanies herpetic outbreaks is bad enough. Start killing nerve cells - which will cause widespread nerve inflammation - and you can count on that neuralgia being significantly worse, and it won’t stop when the virus is cleared.
Almost no viral diseases can be cured. In some cases you can treat the symptoms, or help the immune system fight them off a little more effectively, and you can sometimes vaccinate against a disease to protect you before you catch it, but a cure (something that makes the disease go away after you already have it) is a different matter.
A lot of good points have been made, and there are a lot of other criticisms that could be raised, but I only have the time and energy for - and, frankly, am sufficiently perplexed by - this one.
How, exactly, do you propose to “tack a protein strand onto the virus”? Don’t get me wrong, this is easily done in the lab, but what are you envisioning? Would an infected person show up to the doctor and have all of his viruses extracted, modified, and reinjected for the body to take care of? If we had the ability to extract all of the virus, that would kind of take care of the problem. No need to modify or reinject.
Or are you thinking that we would make a modified version of the virus and release it into the world to outcompete the regular version? Because then you’re setting up a case of natural selection, with two competing viruses. One virus is easily found and cleared by the immune system, and the other one isn’t. I’ll let you figure out what would happen from there. HINT: it’s not the eradication of the “difficult to kill” version.
The only other thing I can think of is that the added “protein strand” would act as some sort of vaccine, but then you’re vaccinating against an epitope that doesn’t exist on the native virus.
I genuinely can’t figure out what you’re proposing here, and I’m working on a PhD in biology at the moment.
I though he was suggesting injecting something into the patient that would attach itself to the virus to make it easier for a subsequent treatment to find.
Trouble is, if you could do that then you could skip that stage and just make the treatment find and attach to the virus in the first place, using the same technique that you are proposing for the marker. That is, as the OP acknowledges the virus is effectively invisible, and that’s just as true for whatever marker you want to use as for the treatment.
Plus it’s essentially the same as what our immune system already does. B cells create antibodies, which are proteins that stick to some specific bit of a pathogen. The antibodies flag the pathogen for recognition by other parts of the immune system. Antibodies are “designed” through a sort of evolutionary process that’s far better than any protein design that scientists can do. There are some antibody-based drugs, but those all are modified versions of antibodies originally “designed” by an immune system.
So if the virus hides in nerve cells when it’s dormant is it correct to say that viruses do no damage to the nerve cells themselves?
If this is true then won’t the T-cells recognize the virus infected cells as soon as the virus becomes active and suppress the spread? It seems that while you’re not “cured” the T-cells would keep the virus in check. What am I missing (sorry I failed biology in high school :D)?
That’s what they do, that’s why you have the manifestations when the virus reactivates. But the virus then goes back to stealth hiding mode, and becomes undetected again.
HIV is not the same virus as HSV (not even in the same virus family). Some viruses can indeed be cleared by the immune system, they don’t linger on and on and on. And viruses have a lot of ways of making more copies of themselves (insert into host DNA or not, some don’t even need DNA, some sometimes may recombine with host DNA some don’t mix, etc.).
HIV (a retrovirus) is a problem precisely because it replicates and “lives” in T cells (T lymphocytes). It targets those cells. If the cells in your immune system are screwed up, you have problems.
With HSV (a herpes virus), when it comes out of the latent stage and start producing antigen that is recognized by the body, it is attacked. But it goes back to hiding and stealth mode (in cells that are not involved in the immune system).
This is a great thread! I suffer from time to time from herpes, so I am interested in this topic.
Here is an idea, would this be effective? Since we can’t kill the virus, is it possible to force it to stay in hiding? Could there be some kind of treatment to prevent the virus from reactivating, thus rendering it useless?
Sorry if this is a hijack, but a light bulb went off when I read about the connection between viruses and nerve cells:
Is this why getting chickenpox as a child can manifest itself as shingles during old age? Is the pain of shingles the result of latent chickenpox viruses re-emerging from hiding in nerve cells?
This is extremely generalized, so take it for what it’s worth:
HSV does not damage nerve cells during its latent stage. When it emerges, there is at least some inflammation of the involved nerve cells (specifically, the nerve ganglia near the base of the spine), which can cause neuralgia (nerve pain) during an outbreak. Inflammation, however, is caused by the immune system and not by the virus.
Eventually the immune system picks up on the outbreak, issues antibodies, killer T cells, cytokines, and all the other good stuff, and - for most people - kills off the active virus, leaving only the latent. However, herpes is infamous for flaring during times of physical and emotional stress. During stress, the body releases cortisone, cortisol, and related hormones which suppress the immune system in order to allow the body to focus its resources on whatever the stressor is. That immune suppression allows the virus to “play while the cat’s away”. If the immune system is occupied with a different infection - like a rhino- or adenovirus - HSV can also take the opportunity. It’s why oral herpes sores are often called “cold sores”.
And you want to know something creepy? There’s more and more discussion about how infectious agents - virus, bacteria, protozoa, fungal, parasitic - can alter its hosts behavior. Rats infected with toxoplasosis show unusually risky behavior that often results in being eaten by cats - which then, in turn become infected. There’s a specific fungus which, when it infects an ant, causes it to leave its hive, climb up to a high point, and die - allowing the fungus to produce a fruiting body and spread its spores far and wide. You think humans are immune from this? Many people with herpes report feeling more interested in sex shortly before and even during an outbreak - the period when they are most likely to infect another person.
Is anyone familiar with the cullen lab website. In their FAQ section, they make it sound fairly promising that a cure may be possible. They seem to be leading the research on this topic so it seems legitimate to me. Any comments on this? Is it all just wishful thinking? Is it worth donating a sum of money?
Huh. I googled the Cullen lab, and at first glance they seem to be an entirely respectable academic research group. They do mostly basic research, and it seems that they found something promising and are soliciting private donations to fund preclinical research :dubious:. That’s an extremely… unusual practice in academic research, and frankly it smacks of desperation. That tells me that they can’t convince grant reviewers (i.e. other scientists in their field) or anyone in private industry that their work is worth funding. And that’s not a good sign.
I’m not a virologist , so I can’t speak directly to their work. In general though, “Promising New Treatments!” are almost literally a dime a dozen. Many basic researchers will stumble across something that has a bit of potential for treating some disease. Some will do an experiment or two to demonstrate the clinical potential, usually by treating mice in small numbers. That’s where it seems the Cullen lab is. But the vast majority of little academic “pre-clinical” trials lead nowhere, even if they seem immensely promising and fool-proof from the start.
The biotech/pharmaceutical industry funds much of the research at this level. From a financial perspective, research makes for an extremely high-risk investment. I’d ballpark the odds at 1/1000 – as a crude rule of thumb, 1 in 10 treatments will fail at every stage of development (basic research -> pre-clinical development -> stage 1-3 clinical trials).
If you want, you can give money and know it’ll end up paying for this lab’s research. But keep expectations realistic! You’re not funding a cure. You’re funding early research that has a one in a thousand shot at leading anywhere.