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?


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,


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