Tuesday, September 6, 2011

CCR5-∆32 and Black Plague resistance

David Wright, 42748964

A mutation of the CCR5 gene, delta 32, has been found to be associated with resistance to HIV 1 infection.[1] For total resistance to HIV, the mutated gene must be inherited from both parents.[2]

Figure 1: The CCR5-∆32 mutation results in a non-functional protein that cannot serve as a receptor for HIV. This allows for resistance to HIV infection.[3]

It has been theorised that the mutated CCR5 gene may also have helped resist the Black Plague (Y. Pestis) that terrorised Europe between 1346 and 1352.[4]  If this is the case, it would account for a prevalence of the CCR5-∆32 allele in present-day European humans.
To test this theory, scientists tracked down the descendents of Black Plague survivors from the small village of Eyam in England.[4] This village was selected for two reasons. Firstly, when the outbreak of plague occurred in Eyam in 1665, the vicar of the town imposed a quarantine so as to prevent spreading of the disease to further reaches of the country. This was maintained for five months.[5] Therefore, because the population of Eyam was isolated, it can be assumed that all of the survivors would have been exposed to the virus. Secondly, in 1630 Eyam began keeping a very detailed register of its citizenry.
Historians have been able to use this information to trace the plague survivors’ present-day descendents.
CCR5-∆32 was found in 14% of the DNA samples of Eyam survivor descendents, a genetically significant percentage.[2] These CCR5-∆32 levels were only found to be similar in parts of Europe. In contrast, the allele was found to be absent in Native Africans, East Asians and Indians.[4] This has helped confirm the theory that CCR5-∆32 allele aided in resisting Y. Pestis.
However, a study in which both normal and CCR5-deficient mice were infected with the bacterium Y. Pestis showed no difference in bacterial growth or survival time between the two groups.[6] Either Y. Pestis infection affects mice in markedly different ways to humans, or CCR5 deficiency offers little resistance to the plague. O’Brien, one of the HIV researchers behind the initial Eyam research, believes a suitable experiment to comprehensively test the theory has yet to be designed.[2] However, recent evidence of the CCR5-∆32 allele predating the plague as well as studies of other plague-affected regions have highlighted inconsistencies with the theory that CCR5-∆32 helped resist the Black Plague.[4]
This particular body of research illustrates some of the major difficulties in studying archeogenetics. An open channel of discourse between the various fields of research (e.g. genetics, archaeology, anthropology, etc.) can be difficult to achieve. And even in seemingly isolated, well-observed circumstances, such as the village of Eyam, it is extremely difficult to test scientific hypotheses with any firm experimental control as the passage of time makes it near-impossible to account for all influencing factors. Nevertheless, it is a vital area of research as historical epidemics, such as the black plague, may hold the key to curing modern viruses, such as HIV.

1 Stephens J et.al. 1998, ‘Dating the Origin of the CCR5-∆32 AIDS-resistance allele by coalescence of haplotypes’, Am. J. Hum. Genet, vol. 68, pp. 1507-1515.
2 Educational Broadcasting Corporation, Secrets of the Dead, Educational Broadcasting Corporation, viewed 4 September 2011, <http://www.pbs.org/wnet/secrets/previous_seasons/case_plague/interview.html>
3 Sattentau Q & Samson M, Human Immunodeficiency Virus (HIV), McGraw-Hill, viewed 4 September 2011, <http://accessscience.com/content/Human-immunodeficiency-virus-(HIV)/YB990480>
4 Cohn SK & Weaver LT 2006, ‘The Black Death and AIDS: CCR5-∆32 in genetics and history’, Quarterly Journal of Medicine, vol. 99, no.8, pp. 407-503.
5 Coleman MP 1986, ‘A Plague Epidemic in Voluntary Quarantine’, International Journal of Epidemiology, vol. 15, no. 3, pp. 379-385.
6 Mecas J et. al. 2004, ‘Evolutionary Genetics: CCR5 mutation and plague protection’, Nature, vol. 427, pp. 606.

(Original Article: Cohn SK & Weaver LT 2006, ‘The Black Death and AIDS: CCR5-∆32 in genetics and history’, Quarterly Journal of Medicine, vol. 99, no.8, pp. 407-503.)

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