Andrew Sungwoo Park

Figure 2. HIV Life Cycle

Inhibition of HIV through the CCR5-Δ32 Mutation

CCR5-Δ32 is a mutation in which a 32-base pair region is deleted from the gene that codes for the CCR5 co-receptor. [8] Individuals with the homozygous or heterozygous mutant alleles have immune signal receptors that are shaped slightly different. [5] HIV has to bind to both the CD4 receptor and the CCR5 co-receptor in order to infect the macrophage, but if the co-receptor is shaped differently, the gp-120 proteins of HIV will not be able to recognize it and not bind to it. If HIV cannot bind to the macrophage, the latter processes of the HIV infection would not occur, thus preventing HIV infection right from its initial entry.

Homozygous carriers of the CCR5-Δ32 mutation are completely resistant to HIV infection because their CCR5 co-receptors are non-functioning, while heterozygous carriers are significantly less susceptible to HIV than those that do not carry this mutation. [5][8] Although both homozygous and heterozygous carriers are immune to HIV, safer sex and injection practices are highly recommended because they can still be infected with strains of HIV that do not enter macrophages through the CCR5 co-receptor.  [8] That is due to the fact that HIV is constantly adapting to new environments and evolving.

Theories on the development of the CCR5-Δ32 mutation

History of the mutation

The allele for the Δ32 mutation was dispersed widely at first, spreading over a large geographic area. [2] But over time, the allele frequency increased locally in the northern Europe region due to many selective pressures; and from then on, the mutation remained dormant because it was an unnecessary mutation. [2][3] It was dormant until recently due to the spread of HIV. Because the allele for the Δ32 mutation was so spatially uniform many years ago, there is no geographic restriction on the allele. [2] With time, the Δ32 mutation would definitely spread worldwide.

Selective Pressures

Although the mutation provides people with a resistance to HIV, HIV did not exist in the human population long enough to attribute the mutation to it. That means that there was another selective pressure that is responsible for the distribution of the CCR5-Δ32 mutation. [3]

In the past, many scientists claimed that the Bubonic Plague was the selective pressure that led to the development of the mutation, but that is highly unlikely. The theory is reflective of the intensity of mortality in Europe due to the plague, but the plague did not only affect Europe. [9] In fact, Yersinia pestis, the bacterium that caused the Bubonic plague, spread from Middle East, Africa, and eastern regions. So those regions were probably just as affected by the plague if not more than Europe. This means that the Δ32 mutation could not have been caused by Yersinia pestis, because the high allele frequency for that mutation is located in the northern Europe region and less in the Eastern regions. So many scientists are beginning to think that the Δ32 mutation results from a recurrence of many different diseases such as smallpox and Ebola. [3] Recent studies have shown that the CCR5-Δ32 mutation does not even protect against Yersinia pestis, further proving the fact that the bubonic plague was not the selective pressure for the development of the mutation. [10]