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I read an article about a patient with HIV who also had to undergo leukemia treatment. He had a bone marrow transplant from a donor who had the CCR5 inhibitor mutation, and the virus all but disappeared.
How do genetic mutations work? The article said that you need both parents to have the mutation to get the trait passed on. What gives?
Stranger Personals
Thanks,
X Man Chris
Let's do an experiment together! Copy X Man Chris's question down on a separate piece of paper—using a pen, no scratching out or erasing. After you're done, I bet you have at least a few subtle differences between the original and the copy you made—punctuation, spelling, or even completely different words. Now imagine copying the copy tomorrow and then copying the copy day after day. Eventually, you will end up with mistakes changing the meaning, in a subtle or major way. If your friends make a copy of their own copy every day, eventually you will each have a similar, but distinct, copy of the paragraph.
When DNA (the cookbook for life) is copied in our cells, these sorts of little errors are constantly occurring—mutations. Generally, these are small changes in the genes (the recipe for a protein)—the protein still works, but in a subtly different way. Distributed among the billions of people on the planet are a multitude of these small differences generated by mutations. Occasionally, big changes occur—removals of whole sections—ruining the meaning of the gene and leading to a complete loss of the protein.
Now pay close attention. CCR is short for chemokine receptor. Chemokines and chemokine receptors allow the cells in your immune system to speak to one another; their epic fight against invaders is like a game of Marco Polo. CCR5 is the chemokine receptor found on macrophages—the gobbling-up cells at the front line of your immune system. When you have unprotected sex with someone with HIV, some of the virus makes its way onto mucous membranes or through breaks in the skin. The macrophages do their duty and chase after the virus. When they meet face-to-face, HIV uses its gp120 protein to get into the macrophage through the CCR5 protein—its key to the door. Safely inside, HIV produces billions of copies of itself each day in each macrophage. Being hardy cells, macrophages can survive for years, even while producing the virus. During this massive expansion phase, some of the virus gp120 mutates so that it now binds better to the related CXCR4 protein on helper T cells (the generals of the immune system) than the CCR5 protein on macrophages. Once able to enter T cells, the virus starts killing the more delicate cells off in greater numbers—eventually resulting in AIDS.
People with mutant copies of the CCR5 gene (one from each parent) that block the protein from being made lack the entry door for HIV into macrophages. Thus, they are resistant to infection. Neat.
Exactingly Yours,
Science
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where does this virus that carries this protein come from? Oh yeah how do we dispose of the victims that died from aids.
Also- yes, we do know where it came from. Monkeys.
Or is it more like, as a human's DNA gets mutations, when they rejoin, the DNA elements check themselves. So, the mutation could be in the father's DNA. But, when the mother's DNA sees it, it says, "Nope, that's not right. It should be like this" and the father's DNA says "You're right. Let's fix that." Thus, the mutation is corrected?
Also, how are mutations different than traits like blond hair and blue eyes? Those can be passed on without having both parents have those genetics, though they are generally recessive.
Thank you for responding to my question. :-)
The CCR5 protein product seems to be affected by a single gene, as opposed to some things like height, which is the product of many different genes and external factors as well.
About checking DNA, the cells have lots of mechanisms for checking DNA, but these checks don't catch everything. Mutations in these genes are usually the basis for cancers.
I had a question though. What is the purpose of the CCR5 protein? I'm assuming it has a need. Wouldn't the absence of a working copy of CCR5 put these individuals at a higher risk for certain other diseases? Also, isn't the CCR5 receptor just one of the methods of HIV transmission?
CCR5 is part of the immmune system trafficking and communication system. The funny one works just fine, except as an entry point for HIV. HIV will probably get around it eventually, it mutates incredibly fast (hence the switching from macrophages to T-cells in each individual host).
Also, the treatment could very well have cured this patient of AIDS/HIV. The bone marrow transplant he received allowed his body to produce new white blood cells of all types that would be immune to the virus. Also remember that white blood cells, like every other cell in your body, do not live forever. Indeed, your entire collection of immune cells are replaced many times in your life by new ones. And, finally, you have to keep in mind that, even in a normal person without the CCR5 mutation, the immune system CAN ATTACK AND DESTROY the HIV virus and cells infected with it, it just isn't as likely to occur and the patient isn't likely to be cured because of the virus attacks and dupes the very system fighting it. A fresh set of new immune cells, without the CCR5 receptor, might tip the fight in favor of your body.
And, finally, not everyone with HIV in their system has AIDS.
The why's and how's of co-receptor switching are currently under research, as is how HIV hides in patients on intense anti-HIV therapy. Interestingly, patients treated with experimental anti-CCR5 drugs didn't develop much CXCR4-friendly virus, which is an optimistic sign. Also, since HIV hasn't re-emerged in this patient after a couple years, things look good. However, you're right in pointing out that scientists can't totally exclude the possibility that a CXCR4-friendly variant might crop up someday.
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