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It’s been known for some time that certain people of European descent have a mutation on their CCR5 coreceptor molecule, and people who have two copies of this mutation appear to be completely protected against HIV infection. About 1% of people of European or Caucasian descent have both copies of the mutation, while about 19% have one copy of the mutation, which typically results in a slower progression to AIDS among those who are HIV-infected.
However, people of African or Asian descent have neither of these mutations, which has led researchers to theorize that the mutation is the result of some long-ago viral epidemic that never made its way to Asia or Africa. That has resulted in the theory that the mutation in some way is related to the bubonic plague, which appeared some 600 years ago in Europe.
Michigan researchers have designed a mathematical model that may provide one explanation for why HIV has spread so much more rapidly among heterosexuals in Africa than it has in the United States or Europe. "We wondered if we could explain the severity of the epidemic in Africa," says Denise Kirschner, PhD, an associate professor in microbiology and immunology at the University of Michigan Medical School in Ann Arbor, MI.
Economic factors, inadequate or missing health infrastructures, high levels of sexually transmitted diseases, and too few prevention efforts are all thought to be contributing factors to Africa’s AIDS pandemic. But even when considering these economic and social differences, sub-Saharan Africa’s estimated 20% HIV infection rate is incredibly high.1 "A lot of people come up with different explanations about why the epidemic is so bad in Africa," Kirschner adds. "We wondered if something more uniformly distributed throughout the population would affect it, and our model showed that it could."
The model, which mimicked a heterosexual epidemic, compared the rate of HIV transmission in two populations. One population had no mutations on the CCR5 gene, and the second group had mostly normal plus some heterozygous and homozygous CCR5 mutations. With data provided by UNAIDS of Geneva, Switzerland, the model used demographic data and initial values for infection from surveys conducted in Botswana, Zimbabwe, and Malawi. The model showed how HIV might have spread if the sub-Saharan population contained mutations of the CCR5 gene, Kirschner says.
"We’d see much lower prevalence incidences in Africa if they did have the mutation," says Kirschner. It’s possible that if the mutations were present in sub-Saharan Africa, it might have lowered HIV prevalence there by as much as one-third, she adds.
The study indicates that the overall model predictions are consistent for a wide range of transmission and progression rates. Investigators assumed that lower viral loads correlate with reduced infectivity, which would mean that a population’s proportion of heterozygotes, who are assumed to have reduced viral load, would have a major influence on disease spread.
Investigators considered two possible scenarios of how the presence of heterozygotes of the CCR5 mutation might affect the spread of HIV. In one scenario, the single mutation might exacerbate the epidemic because individuals with it would spend more time in the sexually active population, spreading the virus to others; in the other scenario, the single mutation might lower the viral loads of those who are infected with HIV and therefore decrease the probability of infection. The study’s results suggest that the heterozygote mutation reduces transmission of the epidemic due to reduced viral loads.
"In the end, we could ask the question of how long would it take to select for this protective CCR5 allele in Africa, given we introduced it 50 years ago, and it would take 1,200 years in our model," Kirschner says. "That means HIV likely is a very recently introduced virus into the African population."
In other words, it would take the population of Africa about 1,200 years of battling HIV infection to reach a level of 1% of the population having two of the CCR5 mutations and 19% of the population having one of the CCR5 mutations.
1. Sullivan AD, Wigginton J, Kirschner D. The coreceptor mutation CCR5 32 influences the dynamics of HIV epidemics and is selected for by HIV. Proc Nat Acad Sci 2001; 98:10214-10219.