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Tuesday, September 23, 2008

Did the Romans destroy Europe's HIV resistance?

THE hand of history has a very long reach. It appears that the Roman Empire left a legacy that may still affect modern Europe - those living within its conquered lands are more susceptible to HIV. It could explain why a gene that confers resistance to HIV varies in frequency across the continent.

The gene in question codes for a protein receptor called CCR5. The HIV virus binds to this receptor before entering cells. One gene variant, called CCR5-Delta32, has 32 DNA base pairs missing and produces a receptor that HIV cannot bind to, which prevents the virus from entering the cells. People with this variant have some resistance to HIV infection and also take longer to develop AIDS.

Generally, only people in Europe and western Asia carry the variant, and it becomes less and less frequent as you move south. For example, more than 15 per cent of people in some areas of northern Europe carry CCR5-Delta32, compared with fewer than 4 per cent of Greeks (see map). It is not clear why this is so, since the HIV pandemic - which began in the early 1980s - is too recent to have influenced the distribution of the variant.

However, the changing frequency of the variant reflects the changing boundary of the Roman Empire from 500 BC to AD 500, says Eric Faure at the University of Provence in Marseille, France. When Faure and colleague Manuela Royer-Carenzi investigated possible links between Roman colonisation and the frequency of the CCR5-Delta32 variant in nearly 19,000 DNA samples from across Europe, they found that the gene variant seemed to dwindle in regions conquered by the Romans (Infection, Genetics and Evolution, DOI: 10.1016/j.meegid.2008.08.007).

Alternative theories include the idea that the protective variant originated in Scandinavia, and was spread north and east by the Vikings. But the pattern of Viking migration does not match the current distribution of the variant. Another theory is that a major disease, such as plague or smallpox, created a selection pressure on the gene variant which increased its frequency. But its distribution does not match that of disease outbreaks, either.

So how did the Romans lower resistance across Europe? Some studies suggest that they and other southern Europeans had lower levels of CCR5-Delta32. But Faure does not think that the Romans spread the regular version of the gene into their colonies by breeding with indigenous people. "Gene flow between the two was extremely low," he says.

Instead, he reckons the Romans introduced a disease to which people carrying the CCR5-Delta32 variant were particularly susceptible. As the Romans moved north, this disease killed off people with the variant.

Faure notes that the Romans introduced cats and donkeys into Europe which may have carried pathogens that spread to humans.

What's more, the Romans inadvertently brought with them disease-carrying mosquitoes. Intriguingly, modern people with the CCR5-Delta32 variant are more susceptible to the mosquito-borne West Nile virus.


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