February 1, 2005

People can be infected with many different bacteria and viruses -- but some people get more sick from these bugs than others. Do our genes cause some of that difference?

The answer is yes--different versions of important genes change how easy it is for a person to be infected. The study of these genes might lead to new drugs to block or slow down an infection.

Since the 1980s many people have been afflicted with AIDS, caused by the virus HIV (human immunodeficiency virus). However, not everyone who is exposed to the virus gets sick. Scientists have carefully studied people who seem resistant to HIV infection. What's going on?

The answer comes from an understanding of how HIV interacts with our cells. HIV, like all viruses, can't make new copies of itself without help. It needs to enter cells and use their machinery to reproduce and spread throughout the body.

HIV can only enter certain cells. How does it find the right cells? By special proteins called receptors.

Receptors sit on the outside of cells to receive messages and transmit them into the cell. HIV grabs onto cells that have a receptor called CD4.

Cells with the CD4 receptor are an important part of the body's system for fighting all diseases (our immune system). HIV gradually destroys these cells and cripples the immune system.

It turns out that CD4 isn't enough. Another protein called CCR5 is needed as well. CCR5, called a co-receptor because it works with CD4, is the door that opens to allow HIV to enter the cell.

Many people who are resistant to HIV have a mutation in the CCR5 gene called CCR5-delta32. The CCR5-delta32 mutation results in a smaller protein that isn't on the outside of the cell anymore. Most forms of HIV cannot infect cells if there is no CCR5 on the surface.

People with two copies of the CCR5 delta32 gene (inherited from both parents) are virtually immune to HIV infection. This occurs in about 1% of Caucasian people.

One copy of CCR5-delta32 seems to give some protection against infection, and makes the disease less severe if infection occurs. This is more common, it is found in up to 20% of Caucasians.

Should everyone be tested for this mutation? Not necessarily. It would be dangerous to assume you are completely safe from infection if you have the CCR5-delta32 mutation.

It's not an airtight guarantee of never getting AIDS. Some unusual types of HIV can use other proteins for entering cells. Rarely, there have been people who have two mutant CCR5 genes who have died from AIDS.

Also, CCR5 is not the whole story of immunity to HIV infection. Some resistant people have been found who have two perfectly normal copies of CCR5. So other genes also contribute to slowing down HIV infection, and scientists are busy trying to identify them.

The usefulness of this work is mainly in how it helps us understand how the virus works and points to new possibilities for drugs to treat infection.

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