slowing down virus reproduction

[cameron marical]

how are viruses slowed down? i know that fevers do this to colds, but then why not do this to other viruses too?

 

is there a way to slow down virus mutations? if so, couldnt you cure hiv?

 

thanks.

[GDG]

how are viruses slowed down? i know that fevers do this to colds, but then why not do this to other viruses too?

 

is there a way to slow down virus mutations? if so, couldnt you cure hiv?

 

thanks.

 

Fever tends to slow down viruses (and other pathogens) by changing the body temperature to one at which the pathogen's enzymes do not work as efficiently. May or may not help, depending on the pathogen's sensitivity.

 

The mutation rate of a virus is pretty much a function of the accuracy (or lack thereof) of its polymerase. Off hand, I cannot think of a way to increase the accuracy of a viral polymerase without essentially creating a new virus. Wouldn't help you against the existing viruses. Viral polymerases have probably evolved to be somewhat sloppy, as creating a more diverse population of viruses makes it more likely that they'll survive changing conditions.

 

Stopping HIV from mutating would not cure AIDS, but might make it easier to treat (it wouldn't be as much of a moving target).

[cameron marical]

Stopping HIV from mutating would not cure AIDS, but might make it easier to treat (it wouldn't be as much of a moving target).

______________

 

wouldnt it make the body able to aquire the anitbodys for the virus and kill it? it would be like a common cold afterwards.

 

what makes their polymerases so bad at transcription?

thanks.

[CharonY]

Essentially their RT (reverse transcriptase) do not have proof-reading capabilities. During the reverse transcription step errors are incorporated. If you try to give it a higher fidelity you'll have to add a function (proof reading) rather than inhibiting one. This is generally not feasible.

Moreover, recombination can also occur at high frequency, for instance if a cell is co-infected with different strains.

[cameron marical]

and we do have these proof reading capabilities?

thanks.

[CharonY]

We do not have a reverse transcriptase at all.

[cameron marical]

is reverse transcriptase rna being turned into dna?

[CharonY]

It is the enzyme that polymerises a sDNA strand onto RNA, yes.

[cameron marical]

ok. this may sound stupid but what exactly is an enzyme. ive wiki'd it so many times but just never fully get it. is it really just something that increases the rate of a reaction?

 

thanks.

 

im in basic classes in highschool and i really learn all my stuff on these forums and over the internet. and library.

[GDG]

ok. this may sound stupid but what exactly is an enzyme. ive wiki'd it so many times but just never fully get it. is it really just something that increases the rate of a reaction?

 

thanks.

 

im in basic classes in highschool and i really learn all my stuff on these forums and over the internet. and library.

 

No problem: we all have to learn somewhere

 

An enzyme is a protein that catalyzes a chemical reaction. Catalysts increase the rate of chemical reactions. Enzymes are often particularly good at it, and at catalyzing reactions that are hard to do any other way (like getting only the desired optical isomer out of a synthesis).

 

HIV is not just like a cold (rhino) virus. For one thing, it can spread directly from cell to cell, by causing the cell membranes to fuse together. Second, the main target (or at least one of the primary targets) appears to be the body's T cells. The T cells are the subset of white blood cells (lymphocytes) that are responsible for most of the organizing and activating functions in your immune system.

 

The main way your body clears out a viral infection is by killing the cells that are infected. Since the virus depends on the protein producing machinery of an intact cell, killing the cell deprives the virus of its mechanism for reproduction. In most cases, the cells that are affected are endothelial cells (cells that line your blood vessels, lungs, esophagus, etc.), which are easily replaced. However, if the affected cells are the cells of your immune system itself, well, I think you can see the problem...

 

Most antiviral (or antibiotic) drugs work by slowing down or killing off enough of the invading pathogen that your immune system can catch up and take care of the rest. Once your immune system is depressed that far (by HIV) though, it is hard to come back.

[cameron marical]

and we cant get the anitbodies for hiv because it mutates so fast. so wouldnt finding a way to slow the mutations or completely stop them be the cure for aids?

 

thanks for your help.

[GDG]

and we cant get the anitbodies for hiv because it mutates so fast. so wouldnt finding a way to slow the mutations or completely stop them be the cure for aids?

 

thanks for your help.

 

The problem is that the cells that produce the antibodies (B cells) are relatively dependent on helper T cells ("Th"), which are one of the cell types that are wiped out by HIV. By pre-emptively killing off your Th cells, HIV prevents your immune system from making antibodies (and killer T cells) and mounting a defense. This is where the "immune deficiency" comes from in "Acquired Immune Deficiency Syndrome".

 

The mutation rate of HIV (and all retroviruses) is a function of how accurate its polymerase is when it makes copies of the viral genome. A sloppy polymerase makes errors (mutations) when it copies. To reduce the mutation rate, we would have to force HIV to use a more accurate polymerase, or somehow make its native polymerase more accurate. If we had the ability to do that, it would be easier and more effective to make it stop using a polymerase altogether: this would stop virus replication immediately.

 

You are correct that HIV would be somewhat easier to fight if we could slow down the mutation rate. The problem is that there is no practical way to do it.

[cameron marical]

what about fevers? they slow down viruses overall dont they?

 

as for the helper t cells, could there be a way to increase their defense against hiv? or maybe change the shape or attributes of the helper t cells making hiv useless against them, then the b cells can make all the antibodies fast enough to wipe out hiv before it mutates out of the antibodies, would that work? that would cure it right?

[GDG]

what about fevers? they slow down viruses overall dont they?

 

as for the helper t cells, could there be a way to increase their defense against hiv? or maybe change the shape or attributes of the helper t cells making hiv useless against them, then the b cells can make all the antibodies fast enough to wipe out hiv before it mutates out of the antibodies, would that work? that would cure it right?

 

Fever does help somewhat, by reducing the efficiency of the viral enzymes (unless they have evolved to work at fever temperatures).

 

HIV mainly attacks T cells through a cell surface receptor called CCR5. In some people, the CCR5 protein is mutated: these people are generally resistant to HIV infection. Unfortunately, it is difficult (not currently possible) to change all of the CCR5 proteins in your body to a mutated (immune) form.

 

Also, HIV can also use another receptor, CXCR4, just as well. Both receptors have immune functions, and people who have a mutated variant of one have other immune deficiencies (although not as bad as AIDS!). I don't know of any study in which subjects were deficient in both receptors.

 

Current research includes searching for compounds that block HIV from binding to CCR5, as well as for compounds that prevent the HIV polymerase from working, or the protease that cleaves the HIV polyprotein into the functional separate proteins, as well as other approaches.

 

If you are interested, you may want to try PubMed. Just type in "HIV therapy" in the search field, and you'll get a list of all (pretty much) the published research in the area.

[Mr Skeptic]

The problem is that the cells that produce the antibodies (B cells) are relatively dependent on helper T cells ("Th"), which are one of the cell types that are wiped out by HIV. By pre-emptively killing off your Th cells, HIV prevents your immune system from making antibodies (and killer T cells) and mounting a defense. This is where the "immune deficiency" comes from in "Acquired Immune Deficiency Syndrome".

 

What if you borrow immune T helper cells (eg from someone with the delta 32 mutation) and have them make antibodies, then inject the antibodies?

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Merged post follows:

Consecutive posts merged

what about fevers? they slow down viruses overall dont they?

 

I think that what fevers do is to slow you down. The virus depends on your cellular machinery, so that also slows them down. Immune cells seem to function well at higher temperatures, and this way have more time to refine their attack.

Edited April 24, 2009 by Mr Skeptic
Consecutive posts merged.

[cameron marical]

What if you borrow immune T helper cells (eg from someone with the delta 32 mutation) and have them make antibodies, then inject the antibodies?

 

i like that idea. but i think that you would have to get the subjects specific hiv, then do that before the virus mutates in the body, then have all the viruses starve before mutation. im not sure how much time you could have. though i could be wrong, wich i hope.

couldnt you just inject the t helper cells with the delta 32 mutation and have them do the job themselves? would our bodys know the difference and try to fight the foreign helper cells instead?

Edited April 24, 2009 by cameron marical

[GDG]

What if you borrow immune T helper cells (eg from someone with the delta 32 mutation) and have them make antibodies, then inject the antibodies?

 

Not sure exactly what you're proposing here. It is possible to make recombinant antibodies: for example, you can inject HIV antigens into mice, collect the plasma cells that make suitable antibodies, and clone the antibody genes into essentially "human" antibodies. The problem is that the resulting monoclonal antibodies have proved not to be effective. Antibodies are great for mopping up bacteria and fungi in extracellular spaces and the circulation. For viral infection, cell-mediated cytotoxicity seems to be the most effective control. While antibodies would take some of the viral particles out of circulation, it is much harder to get substantially all of the virus out. And, of course, in the case of HIV this would drive evolution of the virus into forms to which the antibodies don't bind.

 

If you're proposing administering donor T cells to an AIDS patient, generally you get what is called "Graft vs. Host Disease" -- the fresh T cells see everything in your body as "foreign", and attack everything in sight. To the extent that you still have some functional native T cells of your own hanging around, they would recognize the del32 T cells as foreign, and attack them (although you would probably completely purge the bone marrow first, to prevent this).

[cameron marical]

could you clone the cells of the delta 32 to make it a match to yours? would that stop Graft VS Host Disease?

[GDG]

could you clone the cells of the delta 32 to make it a match to yours? would that stop Graft VS Host Disease?

 

I'm not sure exactly what you're proposing there. Probably the easiest thing to do would be to replace your native CCR5 receptor with the delta32 version by gene therapy ("easiest" only in theory: gene therapy still has a number of bugs). The problem with using donor T cells is that the T cells "learn" what is foreign and what is not, during their maturation process. It is thought that T cells are exposed to most "self" antigens in the thymus, and that T cells that strongly react to self antigens are eliminated immediately (because otherwise you would have auto-immunity -- where the immune system attacks your own body).

 

You would need to start with immature T cells, pre-thymocytes that had not been through the thymus yet. Those cells could presumably mature into functional T cells with CCR5del32, but you would still have the problem of (a) HIV direct spread from cell to cell by membrane fusion, and (b) HIV entry by CXCR4.

[cameron marical]

If someone was to find a way to slow virus reproduction down while co-evently doing nothing to the cells of the body, that would be a cure for hiv and many other diseases right?

 

 

Also, what are the effects of lower temeratures on viruses?

[GDG]

If someone was to find a way to slow virus reproduction down while co-evently doing nothing to the cells of the body, that would be a cure for hiv and many other diseases right?

 

 

Also, what are the effects of lower temeratures on viruses?

 

Slowing down viral reproduction generally helps, but does not guarantee a cure. There are some pathogens that replicate very slowly, and evade the immune system by other means. TB, for example (not a virus, but bear with me), reproduces very slowly (it can take weeks to culture the bacterium), but has a thick mucopolysaccharide coat that protects it from the host's immune system. Other pathogens secrete proteins that turn off immune responses directly.

[cameron marical]

Are their any other methods of slowing virus replication other than a fever?

[GDG]

Are their any other methods of slowing virus replication other than a fever?

 

The tactics that your immune system use include:

• shutting down protein production (this is one of the functions of interferon); and
  
• killing off infected cells (this is what cytotoxic T cells do)
  

 

Approaches used by drug companies include:

• inhibiting the activity of any viral protein, thus interfering with its life cycle;
  
• blocking virus entry into host cells: if the virus cannot get inside, it cannot replicate