生物谷报道：Published online: 11 March 2005; | doi:10.1038/news050307-15
专家争论是否由天花或者瘟疫有此荣誉！
中世纪的欧洲瘟疫的大流行似乎应该有意想不到的效果，使10％今天生存下来的人具有可抗HIV的侵染，但是是什么疾病导致产生抗HIV的免疫性？研究者认为是瘟疫，而反对者确认为是天花！但清楚的是某些条件促进了基因发生突变帮助产生对HIV的抗性。突变产生影响白细胞表面蛋白CCR5，阻止了HIV进入 这些细胞，进而毁坏免疫系统。
详细内容参见如下：
Deaths from plague in the Middle Ages may have left more people with a gene that guards against HIV.
Experts argue over whether smallpox or plague should take the credit.
Devastating epidemics that swept Europe during the Middle Ages seem to have had an unexpected benefit - leaving 10% of today's Europeans resistant to HIV infection.
But epidemics of which disease? Researchers claimed this week that plague helped boost our immunity to HIV, but rival teams are arguing that the credit should go to smallpox.
What is clear is that something has boosted the prevalence of a mutation that helps protect against the virus. The mutation, which affects a protein called CCR5 on the surface of white blood cells, prevents HIV from entering these cells and damaging the immune system.
Around 10% of today's Europeans carry the mutation, a significantly higher proportion than in other populations. Why is it so common in Europe? One possibility is that it favours carriers by protecting them from disease. But geneticists know that the mutation, called CCR5-32, appeared some 2,500 years ago - long before HIV reared its head.
"You need something that has been around for generation upon generation," explains Christopher Duncan of the University of Liverpool, UK, who led the latest analysis. Plague fits the bill, he and his colleagues conclude from a mathematical modelling study published in the Journal of Medical Genetics1.
"You need something that has been around for generation upon generation."
Christopher Duncan, University of Liverpool, UK
Repeated outbreaks
Duncan's team points out that when the Black Death first struck, killing some 40% of Europeans between 1347 and 1350, only 1 person in 20,000 had the CCR5-32 mutation. As the centuries wore on, repeated outbreaks, culminating in the Great Plague of London in the 1660s, have occurred in tandem with rises in the mutation's frequency.
Other experts are not convinced, however. A similar study2 published in 2003 suggests that it was smallpox that boosted the mutation's frequency. "Smallpox would still be my favoured hypothesis," comments Neil Ferguson, an infectious disease expert at Imperial College in London, who was not involved in the study.
Duncan counters that smallpox has only been a serious threat in Europe since the 1600s, which may not have been enough time to have such a big genetic effect. But Ferguson argues that the influence of smallpox over the centuries may have been underestimated, because it largely affected children.
"Smallpox would still be my favoured hypothesis."
Neil Ferguson, Imperial CollegecLondon
"Smallpox seems the most parsimonious explanation," he adds. He points out that one major problem with Duncan's plague theory is that it requires a rethink of how plague was caused. If those with a virus-blocking mutation were more likely to survive, it follows that plague would have been caused by a virus. But the conventional view is that the plague epidemics of the Middle Ages were caused by a bacterium, Yersinia pestis.
Rats off the hook
Duncan admits that his theory is difficult to prove. But he argues that the outbreaks are easier to explain if one assumes that plague was passed directly from person to person as a virus, rather than the 'bubonic plague' that was caused by bacteria carried by rats and their fleas. "Rats are absolutely in the clear for Europe," he argues.
If that's true, then Duncan can explain not only the mutation's average levels in Europe, but also the fact that people in Finland and Russia have the highest level, around 16%, whereas a mere 4% of Sardinians possess it.
He points out that outbreaks of feverish viral disease continued in Scandinavia and Russia for far longer than in the rest of the continent, reinforcing the mutation's status as a valuable asset. "It was mouldering on until about 1800 in northern Europe."
References
1. Duncan S. R., Scott S. & Duncan C. J. J. Med. Genet. 42, 205 - 208 (2005).
2. Galvani A. P. & Slatkin M. Proc. Natl Acad. Sci. USA 100, 15276 - 15279 (2005).
中世纪瘟疫提高了欧洲人“抗艾”能力
据路透社报道，2005年第三期英国《医学遗传杂志》公布的一项研究结果称，中世纪时代欧洲大陆长期暴发的出血热流行病为如今的欧洲居民提供了生物“选择压力”，这使得当今10%的欧洲居民对艾滋病病毒具有非常强的抵抗力。
在被命名为CCR5的细胞感受器中，一种被称为“Delta-32”的突变基因可保护人体免受艾滋病病毒感染，和其他大陆居民相比，这种突变基因在欧洲居民人身上更为常见。
科学家们以前认为，这种基因突变现象十分普遍，因为它可以保护人们不受黑死病或天花流行病的侵袭，而正常CCR5细胞感受器中的基因突变被认为不具有这项功能。
英国利物浦大学的科研人员通过电脑模拟公元1000到1800间欧洲人口统计数据发现，出血热流行病的盛行，加速了这种基因突变现象出现的频率，从过去黑死病流行时期的2万分之一增加到了当前的10分之一。
研究人员指出，早从公元前1500年起，致命性的病毒性出血热就已经开始在尼罗河谷出现了；公元前700-450年期间，这种疫情又在美索不达米亚平原流行起来；公元前430年，雅典也出现了出血热；公元541-700年间，东罗马帝国也暴发了出血热疫情；公元627-744年间，早期的伊斯兰帝国流行起出血热疫情。英国科研人员解释说，1347到1665年间，欧洲大陆持续发生出血热疫情，CCR5细胞感受器成为出血热病毒侵入人体的入口。
科研人员指出，尽管1665年伦敦大瘟疫高峰早已经成为历史，但出血热这种疫情并非彻底消失了。
利物浦大学生物学院教授克里斯托弗·邓肯最后表示：“1665-1666年伦敦出血热大瘟疫并没有完全消失，后来继续在瑞典、丹麦、俄罗斯、波兰和匈牙利等国流行，这种情况一直持续到1800年。
出血热瘟疫的继续存在，为人类基因突变提供了连续不断的选择压力，这就是今天CCR5-Delta-32突变基因在斯堪的纳维亚和俄罗斯出现频率最高的原因。”
