MadSci Network: Genetics


Date: Mon Sep 28 10:52:53 1998
Posted By: Mike Conrad, Post-doc/Fellow, Microbiology, UNC
Area of science: Genetics
ID: 901671613.Ge

I presume you are talking about people with a homozygous deletion in the chemokine receptor gene, CKR5 (or CCR5). That means that part of the gene has been literally cut out (deleted). Thus the protein product of the gene, a chemokine receptor, is missing a critical piece and so it is inactivated.

This chemokine receptor allows proteins to be transported into the lymphocyte and when the HIV virus attaches to the CD4 receptor on the lymphocyte (in this case a monocyte) it needs a working CKR5 to get into the cell. Genes usually come in pairs. About 1% of people of European descent have a deletion in both copies of their CKR5 gene, so their monocytes have no CKR5 and HIV can't get into their monocytes. This leaves them generally resistant to getting infected by HIV-1, or if they do get infected, the AIDS disease spreads more slowly. Note that even if someone is CKR5 deleted, this person can NEVER be sure that they are 100% resistant to HIV-1. HIVs can come up during the course of an infection which directly infect T lymphocytes. People who are CKR5 deleted HAVE gotten AIDS, presumably from being exposed to these T lymophocyte tropic HIVs.

Why the racial and geographic distribution of the CKR5 deletion? Apparently the bacteria Yersinia pestis (bubonic plague) also attaches to the CKR5 receptor. Plague comes in areas with rats, fleas, and cities. Europe has had rats, fleas, and cities for at least a thousand years or so and it has been repeatedly swept by plague epidemics. Early on, someone with a CKR5 deletion must have been born. They were resistant to plague so they and their children survived. Hence now we have the geographic (Europe) and racial distribution (Caucasian) of the CKR5 deletion in the genepool.

Note that genetic mutations and deletions are random and happen by chance. There's probably a new mutation in everybody (or every few people) in one of our 100,000 genes. And occasionally a mutation in the CKR5 gene will occur, and of course it happened in the past. In the population, this deletion you asked about is the most common, but there are other mutations in CKR5, and each one came from some "founder" way back when. And long term survivors to HIV occur in all races and locations, so that gives hope that other ways will be found for the body to elude HIV. But of course, prevention - avoiding contact with HIV - remains the best cure.

Mike Conrad.

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