Biological Control of HIV: How Thousands of Years of Plague Created Virus Immunity

HIV AIDS

The Human Immunodeficiency Virus or HIV epidemic became a worldwide problem in the late 1970s. The virus jumped from primates to humans around the 1920s through the processing of bush meat. The virus spread unrecognized until the 1980s, when the disease was more fully recognized and its virus identified. Globally, HIV has killed 35 million people as of 2015.

Interestingly, however, 10% of the European population is immune to the virus. And scientists have recently figured out why – a mutation.

The mutation of C-C chemokine receptor type 5, called CCR5-delta 32, prevents HIV from binding to the T-helper cell membranes, and therefore blocking the virus from entering the cell. But this puzzled scientists for many years as HIV has not been in the human population long enough to drive such a drastic evolutionary change. The mutation was also almost virtually absent from Asian, American Indian, and sub-Saharan African populations, the last of which being hit hardest by the disease.

Even within Europe there was variation with the highest percentage of mutations in Finland and Russia (16%) and the lowest in Sardinia (4%). So how did this come about?

Simple answer: the plague.

Throughout history, humanity has been plagued by, well, plague.

There was the Plague of Athens in 430 BCE, the Plague of Justinian from 541 to 700 BC, and the plagues of the early Islamic Empire from 627 to 744 BC. The most famous outbreak was the Black Death where an estimated one-third to one-half of the population of Europe died between 1347 to 1351, ushering in the Renaissance Era. Plague also reappeared in Britain in the 1600s during the Great Plague of London where 68,596 people were to have recorded to have died although some estimates say it was closer to 100,000.

Today most people associate the word “plague” with the Bubonic Plague, responsible for the outbreak of the Black Death in the 1300s. The disease was caused by bacterial infection of Yersinia pestis. This bacterium also caused the Plague of Justinian 700 years earlier. DNA analysis reveals that two separate strains of bacteria jumped from rats to humans by way of flea vectors, indicating that rats may be a natural reservoir for pandemic outbreaks of plague.

But Yersinia pestis is a bacterium. So how did it help Europeans arm against HIV, a virus?

Turns out, it didn’t.

Along with plague outbreaks, it is believed that there was a parallel occurrence of viral haemorrhagic fevers. The first account of this disease dates back even before Y. pestis made the jump from rats to humans. In 1500 BCE, 2000 years before Justinian and his plague, viral haemorrhagic fevers were present in the Nile River Valley. The disease reappeared in Mesopotamia from 700 to 430 BCE, as well as in Athens, Justinian’s Roman Empire, and the early Islamic Empire. It continued to appear in Sweden, Copenhagen, Russia, Poland, and Hungary all the way up to the 1800s, which explains the high frequency of CC5-delta 32 mutations in Scandinavian and Russian populations.

It is estimated that because of these viral fever events, by the 1300s, era of the Black Death, 1 in 20,000 people in Europe had the CCR5-delta 32 mutation.

But how does this connect to HIV?

Viral haemorrhagic fevers also use CCR5 as the binding site to infect T-helper cells. Since the delta 32 mutation impairs the CCR5 receptors, the haemorrhagic fever virus is prevented from entering the cell, similar to HIV. Through the process of natural selection, the mutation survived and thrived from the waves of plague, allowing its carriers to pass on their resistance to later generations. And since the virus was concentrated mostly in Europe, it makes sense that the mutation would persist there in higher numbers.

An interesting query to consider – could this example of natural selection be created in the lab? Could scientists somehow mutate the normal CCR5 gene into the CCR5-delta 32 variant to eradicate HIV forever?  As anything that directly affects human health, the morality and cost of such a procedure would have to be carefully considered.

Sources:

  1. https://www.sciencedaily.com/releases/2005/03/050325234239.htm
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1736018/pdf/v042p00205.pdf
  3. http://www.thelancet.com/journals/laninf/article/PIIS1473-3099%2813%2970323-2/fulltext
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185609/
  5. http://www.nationalgeographic.com/science/health-and-human-body/human-diseases/the-plague/
  6. http://www.nationalarchives.gov.uk/education/resources/great-plague/
  7. https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics
  8. https://www.avert.org/professionals/history-hiv-aids/origin
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