How come some viruses lasts years?

Submitted by alttoupvotemyself t3_xwzpm8 in askscience

The question is how can some viruses that aren’t chronic take so long time (Years) for the body to fight off?

So Virus generally to my understanding are just blindly trying to multiply. Our immune defense is trying to stop this. In normal sickness the virus multiplies but after a short while be it a few days or weeks the body’s defense turns the tide and the virus is defeated. The other extreme is the virus goes rampant and then kills the victim as the defenses failed to hold back the virus. I understand in chronic cases the virus is able to go dormant and hide to avoid the immune defence to at times wake up and cause a new outbreak. But the outbreaks gets defeated just so the dormant virus isn’t found and exterminated. But there are viruses that lasts for a long time where the virus still gets defeated permanently. How come it takes so long time yet never the virus takes totally over or the immune defense does? Is it a long time of “stalemate” where the replication of virus is about as large as the immune defence can keep up killing it, causing a “stable” state. Take HPV warts for example. They have strains that aren’t “permanent” but can take years before fought off.

Is some of my understanding wrong or how come it take so long? What happens after years that suddenly tips the tide? And how come if it isn’t defeated before then it doesn’t spread more? Like I’m case of HPV to all skin cells?

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iceyed913 t1_ir9hkx1 wrote

cause they integrate into your dna via reverse mrna transciptase. this is only a concern with specific viruses types and only when you get older and immune system gets weaker. thinking of aids or herpes family viruses here. edit: also stress due to exhaustion will deplete your natural dna restoration mechanisms and immunity against cells showing abberant behavior, so then you get flare ups causing pathological damage to tissues

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The_RealKeyserSoze t1_irbouty wrote

Just to clarify Herpesviruses are not retroviruses and most herpes viruses don’t integrate with the host genome (the few that do use a completely different mechanism than HIV). Herpes tends to hide out in cells that are left alone by the immune system allowing for chronic infection.

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Tim_the_geek t1_iraky47 wrote

I thought mRNA doesn't affect/change your DNA. Can you explain the mechanism?

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iceyed913 t1_irav3hd wrote

mrna transcriptase makes dna into mrna. reverse transcriptase makes mrna into dna. this gets laced into the nucleus dna via a few other enzymes. im a bit rusty on the specifics but there are a few mechanisms through which this proces can take place throughout all organic life. its how bacteria exchange antibiotic resistance genes and such

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Tim_the_geek t1_irbeebl wrote

What is required for reverse transcriptase? mRNA, and enzyme and a cell? How long is the new genetic code part of that DNA? Forever?

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The_RealKeyserSoze t1_irbmwgs wrote

Reverse transcriptase is a viral enzyme. Normally you cant go RNA-> DNA. Retroviruses use it, there are only two retroviruses known to infect humans: HIV and HTLV. Both of those viruses manage to keep their genes integrated in at least some cells forever, which is why curing HIV is very difficult despite effective treatments that prevent viral replication.

However other viruses that cause persitent infection do not use reverse transcriptase. Some (like HPV) can integrate with the genome but they are DNA viruses integrating with DNA (and not retroviruses). Herpes viruses generally dont integrate with the genome but a few can (again DNA to DNA), but chickenpox (a herpesvirus) as well as herpes simplex (the one you probably think of when you think of herpes) infect nerve cells and hide out in them as the immune system usually does not attack nerves, so they persist through a completely different mechanism from genome integration.

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B_r_a_n_d_o_n t1_irc7kp9 wrote

>> How long is the new genetic code part of that DNA? Forever?

​

Yes, forever.

We have quite a lot of DNA injected into our cells from viruses in the distant past.

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iceyed913 t1_irbi402 wrote

im pretty sure there is an error correction mechanism that removes genetic sequences which seem out of place or mutations. no idea how likely it is to always work, but infected cells are cleaned up through autophagy, programmed apoptosis (this is like murder and suicide), so viral sequences will most likely be removed at some point. chronic viral infections like aids and herpes are forever though. edit: i do not have a degree or anything in this area, so if you want to know more im sure youtube has simple videos explaining these things

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Agood10 t1_irde2ek wrote

Herpes isn’t a retrovirus. Nor is HPV, per OP’s specific example.

HIV and HTLV are the only circulating retroviruses known to integrate into the human genome. The only example of a non-retrovirus integrating into host DNA that I’m aware of (not to say there aren’t others) is HPV, which can unintentionally become integrated into host DNA due to DNA damage and subsequent repairs that incorporate the viral DNA. This isn’t so much a cause of poor clearance though, at least for HPV, as the integrated DNA isn’t capable of producing viable new HPV virions.

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Electronic_Health22 t1_irbwgis wrote

Because your immune cells aren't good at killing off pathogens that have long life cycles and slowly replicate. This is because your immune cells target foreign proteins and when the virus doesn't make a whole lot of new protein, there's not a lot for your immune cells to recognize. This is called a dormant stage. HSV does this by hiding in the dorsal root ganglia which is an immune privileged site.

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Level_Rule2567 t1_iraknu2 wrote

Hi, just here to make some corrections. As I understand, yes, there are some viruses that reverse transcribe and then integrate into the host DNA, this is a really good example of virus that “hide” from the immune system. They usually activate or make more damage when the infected person goes trough a period of immune system weakness. This kind of viruses are called retroviruses. HPV is not a retrovirus, and it uses a different hiding strategy. This virus can “hide” from the immune system getting kind of dormant in the brain cells. When your immune system is weak, it activates again. Viruses are not really considered living organisms (well, it depends who you ask) but they pretty much follow evolution rules, just that much faster, because of the type of molecule they use as genetic code (RNA virus genomes are much less stable than DNA viruses) and because generally, the polymerase protein they use to make new copies of the genome lacks what is called “proofreading” activity, making them commit more “mistakes” when copying their genome. So when you get virus multiplied, you don’t have millions of copies of the exact same virus, but you got millions of viruses that are really similar, but not exactly the same. Some of this mutations makes some of these new viruses more resistant to certain actions of the immune system, so the original virus may get eliminated, but the mutated virus don’t. This process repeats multiple times, so your immune system constantly recognizes and find new ways to fight the new variants, but the new variants keep appearing all the time. At the end, who wins this battle and the time it takes all this to happen gets you the final result. Maybe someone can contribute more on this issue, or maybe correct something, but that is pretty much what I know. Hope I helped you.

Edit: someone make me notice, HPV does not infect brain cells, I was confusing it with HSV-1.

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Agood10 t1_irdc7ff wrote

The strategy is going to be somewhat virus-specific.

As one user noted, retroviruses go dormant by integrating into your own genome, at which point it becomes nearly impossible to rid them completely. External stimuli causes your own cells to express the integrated viral genome, leading to production of new virus. HIV is going to be the most common example in humans.

Other viruses, like herpes, infect so-called immunoprivileged cells that are considered too vital to be damaged in an immune response. In the case of herpes, nerve cells become infected where the virus can lay dormant more easily, as nerves are immunoprivileged cells. Some viruses, like Zika and Ebola can infect the testes which are also privileged sites.

Another general strategy is for the virus to simply hang out in the nucleus of a cell and stop replicating. The nucleus is a nice place for a virus to hang out because (to my knowledge) there aren’t really any proteins involved in recognition of pathogens there. Such proteins are typically in the cytoplasm, within endosomes, or on the cell surface. Furthermore, if a virus stops replicating then there’s not much material for our immune system to recognize. That I know of offhand, herpes, HPV, and cytomegalovirus (and probably MANY others) all employ this strategy.

Most viruses that go latent also express proteins or RNAs that inhibit our body’s ability to recognize pathogens. These come in many different forms but as an example HPV expresses E6 and E7 proteins which cause the infected cell to express fewer genes involved in viral clearance. Another example is how ebolavirus VP35 protein blocks the RIG-I receptor (which recognizes viral RNA)

Last mechanism that comes to mind is that some viruses simply infect areas that aren’t easily accessible by our immune system. HPV infects the epithelia of the uterus in a particular region that has very high cell-turnover rate. Because epithelial cells are constantly being shed in this region, immune cells can’t really patrol it very efficiently.

Anyways I’m just going off memory with this response so sorry it’s all over the place. Hopefully there’s something useful.

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TheDurrrmanNeighbor t1_iri7kvk wrote

Rumor is that most images you see of viruses are just cross dissection images of bacteria. Most people don’t have an electron microscope or a laser microtome as the equipment costs millions of dollars. Viruses are usually benign and less pathogenic than bacteria. They are usually found as nano cysts in the environment. They don’t mature to other stages if they don’t find a suitable biome. Even within your body they may travel in circulation and not find their suitable biome and just die.

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