At last, a tradeoff for all those plagues and invasions

Research by two British biologists published in the Journal of Medical Genetics suggests that around 10% of Europeans enjoy [immunity to HIV] as a direct result of the series of plagues that swept across the Continent from the Middle Ages onwards.

Biologists have known for some time that people carrying a particular genetic mutation, known as CCR5-delta32, remain free of the disease. The mutation prevents the HIV virus from entering the cells of the immune system.

It is also a continuing puzzle as to why the strains of HIV that have swept through Africa have made much less of an impression in Europe.

The new theory suggests that the CCR5 mutation was a by-product of the European plagues. The proportion of people carrying the natural resistance rises dramatically in Europe and particularly Scandinavia, where the figure is 14-15%. It is relatively low in countries bordering the Mediterranean and not found at all in sub-Saharan Africa, Asia or among native Americans.

-- "How Horrors of the Plague Made Europe Safer from AIDS Scourge," The Times, March 11, 05.

Would you like to know more about how CCR5-delta 32 works? Of course you would!

[The gene works]  by locking out viral infections as they try to enter white blood cells via a chemical "gateway".

-- "HIV Immunity Evolved from 'Ancient Mutant,'" The Telegraph, Mar 11, 05

Would you like to know more about how people stumbled across this CCR5-delta 32/plague link? Of course you would! The Tech Museum of Innovation's handy "Ask a Geneticist" column explains it thusly:

In 1665, the plague hit a small village in England called Eyam. The town quarantined itself to keep the Black Death from spreading into the rest of the country. A year later, the plague had burnt itself out but half of the townspeople were dead. Was there something special about the half that lived?

In 1996, researchers tracked down descendants of the people of Eyam and looked for any mutations they might have in common to explain this high survival rate. What they found was a mutation called CCR5-delta 32.

The CCR5-delta 32 mutation was already known for a different reason—people with one copy of the CCR5-delta 32 mutation are resistant to HIV, the virus that causes AIDS. People with 2 copies are virtually immune to HIV.

Now here's where the story gets interesting. Mice with two copies of the CCR5-delta 32 mutation are not resistant to Yersinia pestis, so you can't conclude that CCR5-delta 32  is the thing that kept people from that particular flavor of nasty death.

Or can you? A controversial theory has arisen that suggests the Black Death isn't linked to Y. pestis, but rather, to an unknown virus. The UK's HERO project suggested in 2001 that there was sufficient evidence to discredit the little bacterium: for one, quarantines didn't work against the plague; for another, the brown rat which purportedly bears the fleas hosting Y. pestis wasn't introduced to Europe until after the plague disappeared; for a third, the incubation period and symptoms sound very similar to virally-transmitted hemorrhagic plagues.

So to sum this all up: there's a genetic mutation linked to people who survived the plague. This mutation doesn't necessarily confer immunity against a bacterial form of the plague. However, it is linked to immunity from viral diseases (HIV, and also smallpox). This suggests that mayhap the plagues that swept Europe aren't linked to Y. pestis, but to an unknown viral agent.

It's a fascinating puzzle. I look forward to seeing how it's solved. And something else I look forward to: how long it is before a commercial test for CCR5-delta 32 is available, and how it'll be used. Will people test themselves in an effort to appraise sexual risk? Or will insurance companies use it to calculate a customer's risk factors?

Comments

[Shotrock]

PBS' "Secrets of the Dead" did a whole episode on this topic last year. It was fascinating. One of the examples they gave was a gay man whose partner had died from AIDS very quickly in the early years of the disease (1985 or something). He figured he was doomed, and then . . . nothing happened. Not even HIV+. Nada for the past two decades. He is of British descent, so they tested him and voila! CCR5-delta 32.

[Cori]

I saw the same show as Shotrock. I think they even injected him with HIV, and... nothing. It was incredible.

[ginger]

There's also the possibility that the CCR5-delta32 variant is linked, that is, physically proximal to, the gene responsible for whatever trait was relevant to plague immunity. When chromosomes overlap and exchange material during recombination, adjacent genetic material travels together, so some genes are more likely to be found together than other combinations of genes for reasons other than function and Darwinian selection. It's not as satisfying an explanation, from a storytelling perspective, but it is a common phenomenon in genetics - it's the most common explanation for the association of things like pigmentation with disease susceptibility or resistance.

Side-note: No human has ever been or will ever be injected with HIV as part of a medical experiment in Europe, the US or Canada. I think that his T-cells were grown in culture and exposed to HIV-1 and it couldn't enter the cell.

Another side-note: CFTR, the cystic fibrosis transmembrane conductance regulator, and of course sickle cell trait are cases where a single copy of the mutation confers advantage in infectious disease (respectively, cholera and malaria) but a double copy can prove fatal before reproduction. This is known as the heterozygote advantage and is very satisfying indeed from the storytelling perspective, or would be if we could only figure out where the selection pinchpoint events had been!

[Lisa]

Ginger, you brought some serious science there, and that is SO COOL.

So I'm guessing the possibility of physical proximity/overlapping might explain why we don't have a "test your genes for immunity!" test yet?

[ginger]

That, and I'm guessing the whole liability thing with false negatives. (And false positives, for that matter.)

The proximity phenomenon is called linkage or cosegregation, since I forgot to say that.

[Trisha Kelly]

Hello,

Do you know what blood type this man that is immune to HIV is? 1 in 7 caucasians in Europe is RH- blood type. I have heard that RH- blooded people have higher immunity.5-15% of people in the world are RH-, mainly caucasians. The ones that are other minorities are not really RH- but they have a silent or weak D(RH) positive antigen in their DNA and red blood cells. They are labeled RH+ when donating but RH- when receiving blood.

Blood type and RH factor may correalate with the mutated gene that keeps some people from contracting HIV and AIDS no matter what.

Sincerely, Trisha Kelly