Researchers Modify T-Cells, Make Them HIV Resistant 171
DieNadel writes to share that naturally occurring proteins called "zinc fingers" are being used in a new approach to AIDS treatment. Using modified T-Cells with the zinc fingers, researchers at the Pennsylvania School of Medicine have shown a reduction in viral load in mice. "'By inducing mutations in the CCR5 gene using zinc finger proteins, we've reduced the expression of CCR5 surface proteins on T cells, which is necessary for the AIDS virus to enter these immune system cells,' explains first author Elena Perez, MD, PhD, Assistant Professor of Pediatrics at Penn. 'This approach stops the AIDS virus from entering the T cells because it now has an introduced error into the CCR5 gene.'"
Zinc finger, matrin type 3 (Score:0, Informative)
This gene encodes a protein containing three zinc finger domains and a nuclear localization signal. The mRNA and the protein of this gene are upregulated by wildtype p53 and overexpression of this gene inhibits tumor cell growth, suggesting that this gene may have a role in the p53-dependent growth regulatory pathway. Alternative splicing of this gene results in two transcript variants encoding two isoforms differing in only one amino acid.
Worst summary ever... (Score:5, Informative)
Talk about completely misreading even the one paragraph blurb. Zinc fingers are a large group of protein sub-structures which are used to interact with DNA. This group used them to induce a specific mutation which now seems to be HIV resistant How long this will last is really up in the air though, HIV and all other RNA viruses evolve very quickly.
Re:law of unintended consequences... (Score:5, Informative)
Some people are born with a mutation on their CCR5 gene and therefore do not have a working CCR5 receptor on the surface of their T cells. These rare individuals are immune to HIV infection and seemingly are not affected by the non-functional CCR5 protein. The zinc finger approach aims to mimic this natural immunity.
It would appear that these surface proteins are "superfluous", or at least not really necessary.
Re:This is probably good news (Score:5, Informative)
This does not make the T-cell invisible to HIV, it sets a trap.
T Cell (in sexy voice): How about it, Mr. HIV, do you want to come into my place?
HIV: Om nom nom let me put my arms around you baby... wait, where the fuck do I put my left arm? I can't penetrate without both arms around you!
T cell: All your binding proteins are belong to me.
HIV: I'm going to go hit on someone else. Let go of my right arm, you bastard!
T cell: Om nom nom
Well ok, it's a stretch, the T cell doesn't eat the virus at the end.
But the zinc fingers don't disguise the T-cell, they keep the T-cell from expressing one of the antigens on its surface. So instead of the two binding sites needed for the T-cell to be infected, it only shows one.
Re:law of unintended consequences... (Score:5, Informative)
T-cells are part of the immune system, and perhaps you remember this recent infamous TGN1412 experiment involving T-Cells [wikipedia.org]
Re:law of unintended consequences... (Score:3, Informative)
Yes, that's it. The article abstract is a lot more intelligible than the press release:
http://www.ncbi.nlm.nih.gov/pubmed/18587387 [nih.gov]
They're using Zinc Finger Nucleases:
http://www.zincfingers.org/scientific-background.htm [zincfingers.org]
to target and disrupt the CCR5 gene.
Re:law of unintended consequences... (Score:4, Informative)
Well, I am no AIDS expert but from what I understand is HIV does not really kill anybody. AIDS the resulting condition of HIV, is Auto Immune Difficency Sydrome. Basically you immune system stops working and all the other little virus out there take over start to take over all your other cells and with nothing to stop them; that kills you.
So if you screw-up someones immune system in the name of HIV proofing and that causes it to not work then they will have AIDS anyway even if you do manage to kill off the HIV infection. So yea if it turns out these things are "important" you might destroy the immune system faster then HIV would have.
Re:This is probably good news (Score:3, Informative)
As for changing the genetic code, that's not what you're doing. Instead you are putting out a honeypot to attract the virus. The virus can still infect normal cells, but the modified cells can't be infected -- if you have enough of them, then the normal cells can go about their business. Here's a very simplified model:
Say each generation of HIV has an infection success rate of 50%, and produces three viruses when it lyses its host cell. Each generation would then result in a 50% increase in number of viruses (N*0.5*3). Let's say that you have a 1:1 ratio of normal cells to modified cells. Any viruses that try to infect the modified cells fail, and are taken out of circulation. Now each generation will have a population of only 75% of the prior generation (N*0.5*0.5*3). You can practically get rid of the virus over many successive generations.
* By not possible, I mean very very unlikely. It would require wholesale change of the virus structure.
They're chemokine receptors. (Score:1, Informative)
CCR5 is a receptor for a class of signaling molecules used to coordinate action between T cells, other white blood cells, and other cells (like endothelial cells) that sense infection.
You can buy mice that have had CCR5 nuked entirely. They're slightly more susceptible to fungal and viral infections (HIV is an exception because it actually uses CCR5 to get into the cell), and slightly more resistant to damage caused by immune system malfunction (like asthma).
The reason they're not totally immune-disabled is that the CCRs are highly redundant. Most of the CCR5 signals will also be picked up by CCR1, CCR3, etc. Which is not to say this treatment is guaranteed to work (TGN1412 worked great in monkeys, and then killed people), and hacking the CCR5 gene in every cell in the body is not really feasible, but it's still interesting.
Nature does it too... (Score:3, Informative)
Re:Worst summary ever... (Score:1, Informative)
Even worse than that is the reference to the "AIDS virus". HIV is the virus. AIDS is the resulting condition.