Hiv

Discussion in 'Biology & Genetics' started by Trilobyte, Jul 29, 2005.

  1. Trilobyte Registered Senior Member

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    If it is a retrovirus (RNA-based) like some other curable viruses, is there a reason why there should not yet be a cure? (by resistant indivuals giving serum containing antibodies, or vaccination using a 'dead' or damaged HIV virus ie one that can't replicate)

    Is it just a matter of time before the antibody can be created? I am aware of the higher mutation rate of RNA retroviruses allowing it to avoid full elimination by one antibody type alone, but surely there is not as much variation as that of the common cold bacterium?

    Also, if the virus remains inactive for years then surely this is enough time for the immune system to find an effective antibody naturally. ( it only takes approximately two weeks maximum to cure a current common cold strain )

    Is it a matter of 'time required to find a cure' or is there some extra, abnormal difficulty? Lack of info perhaps? For example; they are not yet aware of the exact process by which HIV kills white blood cells.
     
    Last edited: Jul 30, 2005
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  3. Hercules Rockefeller Beatings will continue until morale improves. Moderator

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    I’m no immunologist/microbiologist, but I’ll make these comments…

    I do not think you fully appreciate the lifecycle of a retrovirus. The majority of the life cycle of a retrovirus is spent as DNA inserted into the genome of the infected cell. Whilst the virus is present as DNA in the host genome, there are no viral proteins for the immune system to recognize. The virus (in integrated DNA form) is safely tucked away from the immune system inside the nuclei of cells and cannot be recognized. Furthermore, every time an infected cell divides it unwittingly copies the integrated viral DNA as well.

    The only time there are viral proteins present that can be recognized by the immune system are during the initial infection stage and when the integrated viral DNA finally "decides" to activate transcription of viral polymerases and capsid proteins and sheds new viral particles. Retroviruses can lie dormant as integrated DNA in the genome for a long time. In fact, our genome is full of ancient retroviruses that have been there dormant for so long that they have become inactive through mutation.

    In the case of HIV it is very difficult for the immune system to deal with the new particles once they start to emerge because (i) the body is swamped with a huge number of viral particles and (ii) HIV targets a major component of the immune system itself (T cells) and kills these cells when the newly formed particles emerge. HIV-positive people develop AIDS precisely because their immune system is all but neutralized by the emerging viral particles.


    <img src="http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/R/retrovirus_life_cycle.png"><P>
     
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  5. Trilobyte Registered Senior Member

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    [This was just a throw-away assuption I made just to encourage a corrective response. I imagined there would be at least some HIV virus particles remaining (outwith a cell) that had not entered a cell or had emerged from a cell, within the dormant period of many years, on which the yet undamaged immune system could act and find an appropriate antibody. Then when the virus becomes more active, even though the white blood cells are the target host, there would be enough present (non-zero at least) to produce the antibody...but maybe not.]

    Why is it that a vaccination cannot be created by "disabling" an HIV virus (making it incapable of replication, and of entering a cell)?

    You could just mutate/genetically engineer it until it cannot replicate or enter a cell but has all of the other charateristics of the HIV virus.
     
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  7. Hercules Rockefeller Beatings will continue until morale improves. Moderator

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    I thought you might say that, and I was hoping you wouldn't because I don't know the answer.

    Please Register or Log in to view the hidden image!

    I've reached the limit of my knowledge on this topic - we'll have to wait for someone more learned in virology/immunology to come along.....<P>
     
  8. geistkiesel Valued Senior Member

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    2,471
    Trilobyte,
    For your information the so-called "HIV test"is a test for claimed anti-bodies to HIV, or rather protein segments of HIV antibodies. Contradictory you say?
    I suppose so.

    Geistrkiesel

    Please Register or Log in to view the hidden image!

     
  9. remington12ga Registered Member

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    I just wanted to say this is a great thread. Now to get on topic, you all bring very relevant points to the table but there is one very important thing to remember. HIV is a relatively new virus, there is still much more research that can be done on its structure and how it infects. As a Virologist myself, I believe that as with most viruses a cure for HIV is out there but we as a scientific community must be patient and not rush ourselves.
     
  10. CharonZ Registered Senior Member

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    There are several key problems regarding a functional vaccine against HIV. One of them is that the envelope of the virus undergoes rapid mutations, resulting in changes in the glycosylation of the envelope, which masks it from developed antibodies. BTW a comparison with the common cold is hard to make as it is caused by a plethora of different viruses (and sometimes bacteria).

    However, structural analyses of the envelope variants are under way, in the hope of finding conserved regions which are suitable as antibody targets.
    BTW when the first studies showed that antibody based vaccine treatments were ineffective, most switched to T-lymphocyte-based vaccine developments.
    The newer structural studies and immunization experiments in primates revived the interest in antibody based vaccines, though.
     
  11. Trilobyte Registered Senior Member

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    If all white blood cells were eliminated from the body are there sites that can regenerate them from stem cells or can white blood cells only reproduce by mitosis?

    If there are such sites, can you increase the blood concentration of a certain hormone that induces their production? A higher production rate of white blood cells may make the rate at which new antibodies can be developed (naturally) reach a higher rate than the mutation rate of the HIV virus. However the problem is that having more white blood cells for the virus to use as a host means that the number of virus particles will increase...which will increase the mutation rate...hmmm.

    During the dormant period of HIV, presumably not all virus particles exist as the deconstructed form in a white blood cell, since the body is producing antibodies specific to SOME mutations of the virus present. (to draw a conclusion to some points made)

    (Assuming the virus is in an ACTIVE state);
    If you remove the "food supply" of the virus, the white blood cells, then the virus particles behave as if they were just stray fragments of inactive proteins. How about this;

    You constantly replace the blood of the patient with artificial blood (which will have the function of ONLY oxygen transfer) thus ensuring that there are no white blood cells left alive in the patient. (Any small amount of white blood cells remaining will be destroyed by the active HIV virus.) You continue replacing the blood for a sufficient amount of time until you are satisfied there are no white blood cells remaining.( If possible you could chemically kill the white blood cells). Meanwhile the patient is being kept in some kind of sealed clean room, free of nearly all pathogens, and is being given antibiotics. (since the patient will then be highly vulnerable to naturally occurring diseases). The patient stays in the clean room until all of the now inert non-replicating viruses are filtered out of the artificial blood by the liver (and kidneys?), thus completely purging the body of the virus (with easily very high success due to the efficiency of the liver). Then the constant addition of fresh artificial blood is stopped and the blood in time becomes repopulated with the patients own RED blood cells and displaces the artificial blood. (Now the answer to my above question is important) If the white blood cells have a site of production then they will gradually be regenerated to normal levels: as HIV-free, fresh phagocytes and lymphocytes are produced. If there is no site of white blood cell production then you could instead reseed the patient with small populations of screened, HIV-free white blood cells (from the patient's blood that had previously been taken) which would then return to normal concentration in the blood soon enough, by mitosis. A good idea might be to reintroduce phagocytes first (since they are immune to HIV - I think) to increase the chance that all virus replicas are removed from the blood (they would eat the virus particles remaining in small blood capillaries). This process would actually be effective whether or not the HIV virus is dormant or active. The patient would then be cured. It would be a rather stressful (physically) and lonely experience (clean room) but could cure HIV. (This would not work for any other type of virus that infects tissue cells - only things that stay exclusively in the blood.)

    This idea was just off the top of my head but took longer than I expected to explain. Does it sound practical (to the micribiologists/virologists out there)?

    Sorry but I have more things to confirm....

    Do lymphocytes pass on some form of "information" to other lymphocytes to produce more of a successful antibody to increase production? Is the "messenger" the actual presence of an antibody?
     
  12. zyncod Registered Senior Member

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    Yeah, like CharonZ said, HIV is capable of undergoing rapid mutation - probably because it makes about 10,000x as many mistakes during replication as eukaryotes do. And your body is fully capable of keeping HIV under control - except that, after you are infected, the HIV genome (in the proviral state) becomes part of your genome. So really, all it needs to do is keep shedding mutated forms of the virus that can attack new T cells until a new antibody comes along that stops the mutated form. This cycle repeats until your immune system crashes and opportunistic infections (like Kaposi's sarcoma) kill you.

    And as far as your idea, Trilobite, about filtering out lymphocytes, it's a good one, except... Well, first off, it would be very, very difficult (if not impossible) to filter all the T lymphocytes - because some unactivated T cells take months to circulate (if they're sitting in the spleen). That is, assuming you could filter them (I'm not sure how that would be done, practically).

    You would want to do, essentially, a bone marrow transplant, like they do for lymphoma patients, which involves high levels of radiation to kill off most lymphocytes. PBMCs (stem cells from the blood) are injected, and the PBMCs migrate to the bone marrow and start dividing to replace the WBCs. Which is great - it might get rid of the HIV infection. However, the radiation drastically increases chances of cancer later on in life. Also, you lose your acquired immunity to a number of diseases because you've killed off memory B cells (for example, you may no longer be immune to chicken pox, which becomes serious in later life). All these are acceptable side effects for lymphoma patients, because lymphomas (because the cancerous cells circulate throughout the body) are one of the worst cancers you can get, and you probably only have months to live anyway. However, AIDS is now considered almost a chronic disease rather than a death sentence, through the advent of the cocktail drugs, and these side effects would probably not be acceptable for AIDS patients.
     
  13. zyncod Registered Senior Member

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    Oh, and, yes - immune cells do pass on info about what antibodies are successful. Antigen-presenting cells (ie, dendritic cells, macrophages) eat bacteria/viruses, chop them up, and 'present' parts of their proteins on the cell surface. T cells that recognize these proteins are activated by the APCs, and a specific type of T cell called a T helper cell activates B cells that also recognize these proteins. The B cell then starts to make large quantities of antibodies that specifically recognize the virus/bacteria. This is a little simplistic and maybe not so well explained, but I hope it helps.
     
  14. Trilobyte Registered Senior Member

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    What is the form of "memory" in a memory B cell? Does it have a limit or just employ more cells when more storage is required? Does some of the memory wear off in time or do the cells just die/divide?
     
  15. zyncod Registered Senior Member

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    The "memory" in a memory B cell is encoded in the genome. Each B cell, memory or not, produces one specific antibody. A memory B cell is one that has been activated, has divided many times, and has gone back to a semi-quiescent state. The memory B cells are not killed as easily by other immune cells and immediately start dividing very rapidly when they come in contact with "their" antigen again.

    The amount of "memory" available in an organism is a function of how many B cells that recognize discrete antigens there are at any given time.
     
  16. Trilobyte Registered Senior Member

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    What happens if there is a pathogen that does not correspond to any available memory B cells? Do the cells change?
     
  17. zyncod Registered Senior Member

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    If there's a pathogen that doesn't correspond to any regular or memory B cells, then there is no antibody for that pathogen. The B cells (and T cells) snip and move around parts of their genome to make the antibodies and they can't go back or change it once it's done.
     
  18. DwayneD.L.Rabon Registered Senior Member

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    locked
     
    Last edited: Oct 12, 2005
  19. DwayneD.L.Rabon Registered Senior Member

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    Last edited: Oct 12, 2005
  20. Lateralus Registered Member

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    as a medical microbiologist by trade just thought i'd state that inorder to truely understand the many (and I mean many) reasons why a HIV-1 vaccine is not possible and indeed why many anti-retroviral drugs are ineffective requires a serious knowledge of virology. Take it from me more traditional vaccine types such as 'Live-attenuated' or 'whole dead' vaccines are simply no way possibly. If you really seak more advanced knowledge i suggest reading virology and medical microbiology text books and looking at the genetic composition of the HIV-1 virus.
     

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