How to Resist a Virus with Your Genes

You might think that since it is an infectious disease, genetics would not play much of a role in susceptibility to AIDS. This intuition turns out to be wrong, as in fact a person’s genome can affect the course of disease in many ways. These include establishing complete resistance to the virus, setting the amount of virus in the blood in the years following infection, and influencing the impact of HIV on the rate of decline of the T-cell population. Certainly too there is a lot of variation for how resistant a patient is to all the pathogens that actually cause tuberculosis, pneumonia, or cancer.

A great example of this is the Δ32 mutation of the CCR5 gene. Several years after AIDS was first recognized, it became apparent that a small number of Caucasian men were apparently immune to the disease. They engaged in high-risk lifestyles and were unquestionably exposed on multiple occasions to the virus, but never seroconverted to HIV-positive status. Some molecular sleuthing soon revealed that the reason for this is that they are missing a sizeable chunk of the back door that HIV uses to get into T-cells, the CCR5 coreceptor. The frequency of this mutation is up to twenty percent in northern Europeans, though it is essentially absent from Africans.