Gene May Help People Resist AIDS Infection
For some time now, AIDS researchers had noticed that there were certain sectors of the human population that seemed to have varying degrees of natural resistance to infection with the HIV/AIDS virus. Now a new study, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), may have identified a possible genetic mechanism behind that natural resistance, in a finding that breaks new ground both in our understanding of AIDS and of the immune system.
The new study's starting point is a chemical named CCR5, which occurs on the surface of white blood cells and seems to act as a kind of receptor or gateway for HIV infection. Not all people have CCR5 in their cells; if they do not, the AIDS virus apparently cannot infect them. But if they do, the HIV virus attaches itself to the CCR5 on the surface of the white cell, and an infection is underway.
But many people also carry produce a chemical called CCL3L1 that compete with HIV for connection with CCR5. CCL3L1 gets to the CCR5 receptor before HIV, the virus is shut out and that cell is not infected. Whether a generalized HIV infection takes hold, therefore, has not only to do with how much HIV virus is present, but also how much CCL3L1 is present to block the virus.
The study's authors set out to study the gene responsible for producing this HIV-blocking chemical CCL3L1, in order to get an understanding of how it might be involved in the variance in production of the chemical and thus the variance in HIV resistance across the population. Working with a group of over 4000 subjects, including a major cross-section of racial and ethnic backgrounds as well as both HIV-positive and HIV-negative subjects, they determined that while some people had no occurrences of the CCL3L1 gene in their chromosomes, many people had multiple copies.
Duplication of genes is not unusual in itself; people often have additional copies of a gene, sometimes one a mutated form of the other, sometimes two variants inherited from the respective parents. But in the case of the CCL3L1 gene, the researchers found that many people had several copies of the gene, and that the number of copies tended to correlate with the person's racial or ethnic group. HIV-negative African-American adults averaged four copies of the gene, while participants of European descent averaged two copies and Hispanic-Americans averaged three copies.
Further, it was not just a simple equation of the more copies of the CCL3L1 gene one has, the more CCL3L1 one's body produces and therefore the more protection against HIV one has. Rather, the more copies of the CCL3L1 gene a person carried in comparison to his or her ethnic group, the lower his or her odds of being HIV-positive. Still, each additional CCL3L1 copy decreased the risk of infection by 4.5 percent to 10.5 percent, with the percentage varying between different racial or ethnic groups.
A lower number of CCL3L1 genes was also associated with faster progression to full-blown AIDS. Plus the risk of infection and progression was highest for persons with both a low number of CCL3LI genes and variants of the CCR5 receptor that more readily accepted HIV.
These findings, while preliminary, suggest a number of directions for further research to produce effective treatments for HIV/AIDS. It may eventually be possible to perform genetic testing to determine an individual's risk of infection with HIV, or even to develop or tailor a vaccine to take advantage of this genetic mechanism.
