在古代人类遗骸中发现的新型乙型肝炎病毒菌株

New strains of hepatitis B virus discovered in ancient human remains

　

　

　

华盛顿邮报：2018年5月9日

　

在蒙古的Omnogobi举行的集体葬礼。在战场上阵亡的匈奴战士中，有一个携带着古老的乙肝病毒序列。(Alexey Kovalev)

　

基因学家在《自然》(Nature)杂志上发表的一项新研究表明，乙肝病毒至少从青铜时代就开始感染人类。

　

乙型肝炎在20世纪60年代被发现，之后一种疫苗(以及诺贝尔奖)迅速问世。尽管有了疫苗，这种病毒仍然会致人死亡，慢性感染也无法治愈。据世界卫生组织(World Health Organization)的数据，2015年有近90万人死于这种病毒，其中大部分死于肝脏并发症。据估计，有2.57亿人携带这种以肝脏为目标的病毒，可能成为癌症的风险因素。

　

血液中任性的病毒颗粒也会在牙齿和骨骼中传染。在一些古代人类中，病毒被埋在这些坚硬的材料中——直到研究人员打开样本并测序其中的DNA链。

　

这项研究的作者检测了生活在200到7000年前的欧洲和亚洲的304个人类样本，以寻找乙肝DNA。研究人员在25人的遗骸中发现了与该病毒匹配的病毒，其中包括埋葬在蒙古万人坑中的一名战士的骨头。从这些序列中，研究人员产生了12个乙肝病毒基因组。这是人类或脊椎动物样本中发现的最古老的病毒基因组。(不过，加拿大麦克马斯特大学(McMaster University)的进化生物学家亨德里克·波因纳(Hendrik Poinar)预测，这种最高级“不会持续太久”。波因纳没有参与这项研究。)

　

研究小组发现了12个古老的乙肝基因组，其中包括一种现已灭绝的乙肝病毒。为了获得基因序列，研究人员不得不进行分子级的类似于垃圾倾倒的实验。研究报告的撰写者之一、丹麦哥本哈根大学的进化遗传学家埃斯克·威勒斯列夫于本周二接受记者采访时说:“我们已经对我们通常所说的废物进行了筛选。”

　

科学家们使用了一种叫做“猎枪测序shotgun sequencing”的技术，这种技术可以随机切割长链DNA(就像用猎枪子弹炸出来的一样)，然后克隆这些片段。由于大量的DNA，遗传学家可以把有机体的基因组缝合在一起。但是，由于长期死亡的感染和其他污染，猎枪过程产生了大量的非人类DNA，威勒斯列夫和他的同事们通常忽略了这一点。“但现在我们已经开始调查这种废料，”他说。

　

骨头里活捉到的病毒并不是活的。剑桥大学(University of Cambridge)博士生、该研究报告的第一作者芭芭拉穆赫曼(Barbara Muhlemann)说:“为了让大家明白，我们发现的病毒序列是高度碎片化的。”她说，“绝对没有危险”，有人碰一碰骨骼就会感染上古代肝炎。

　

波因纳说，完成这项工作的技术已经存在了大约五年，但它需要正确的样本来实现这些结果。“我认为这是对古代DNA的真正好处，”他说:“科学家现在可以在没有其他物理证据证明病毒存在的情况下，在特定的时间点检测到关键的病毒基因组的存在。”在此之前，寻找古代病毒的工作通常始于对人类遗体的损伤检查，就像在意大利发现的一具有500年历史的长着麻子的木乃伊被发现患有乙肝一样。

　

古老的病毒基因组给科学家提供了感染的大致历史。威勒斯列夫指出，这些历史可以强化假设，也可以抛弃假设。据推测，乙肝病毒起源于新大陆，并在大约500年前传播到欧洲。他说，考虑到样本的年龄，这种想法“肯定是错误的”。

　

瑞典乌普萨拉大学(Uppsala University)进化生物学家亚历山大·苏(Alexander Suh)没有参与这项研究，他说:“看起来，一些古代乙肝病毒与它们的近亲在不同的地理区域出现。”“这让我们得以一窥这种疾病的地理分布是如何随时间发生变化的。”

　

一些古老的肝炎病毒仍然感染着人类。另一个死亡。“一件很酷的事情是它显示了基因型的存在，这些基因型今天已经不再流通了，也就是说，它们已经灭绝了。波因纳说:“我们期待这样的结果，但看到它真的很美妙。”

　

威勒斯列夫说，这项工作是已知的乙肝病毒“可能突变”目录的开始。他说，古老的毒株可能会出现，也可能不会再出现，但对这种病毒过去的适应能力的了解可能会帮助科学家预测未来肝炎将如何变异。

　

在古代人类遗骸中发现的新型乙型肝炎病毒——华盛顿邮报https://www.washingtonpost.com/news/speaking-ofscience/wp/2018/05/09/new strains-- bviruss-discovered -in-ancient-human- /

 

New strains of hepatitis B virus discovered in ancient human remains

By Ben Guarino

May 9

 

A mass burial in Omnogobi, Mongolia. One of these Xiongnu warriors who fell in battle carried an ancient hepatitis B sequence. (Alexey A. Kovalev)

The hepatitis B virus has been infecting people since at least the Bronze Age, according to a new study published in the journal Nature by geneticists who teased the virus from 4,500-year-old human remains.

 

Hepatitis B was discovered in the 1960s, and a vaccine (and Nobel Prize) came swiftly thereafter. Despite the vaccine, the virus still kills people, and chronic infections cannot be cured. Nearly 900,000 people with the virus died in 2015, mostly from liver complications, according to the World Health Organization. An estimated 257 million people carry the virus that targets the liver and can be a risk factor for cancer.

 

Wayward viral particles in the blood also catch in teeth and bones. In some ancient humans, the virus became entombed in these hard materials — until researchers cracked open the samples and sequenced the DNA strands inside.

 

 

The study authors examined 304 samples of humans from Europe and Asia, who lived between 200 and 7,000 years ago, to look for hepatitis B DNA. Researchers found matches for the virus in the remains of 25 people, including in the bones of a warrior buried in a mass grave in Mongolia. From these sequences, the researchers generated 12 hepatitis B genomes. These are the oldest viral genomes recovered from human or vertebrate samples, the authors said. (Though evolutionary biologist Hendrik Poinar, a professor at Canada's McMaster University, who was not involved in this study, predicted this superlative “won’t stand too long.")

 

The team found 12 ancient hepatitis B genomes, including a now-extinct type of the virus. To get the genetic sequences, the researchers had to do the molecular equivalent of a dumpster dive. “We have screened what we normally call the waste product,” study co-author Eske Willerslev, an evolutionary geneticist at the University of Copenhagen in Denmark, told reporters on Tuesday.

 

The scientists used a technique called shotgun sequencing, which shreds long strands of DNA at random (as if blasted by shotgun pellets) and clones the fragments. Thanks to the high volume of DNA, geneticists can stitch together an organism's genome. But the shotgun process churns out plenty of nonhuman DNA, courtesy of long-dead infections and other contamination, which Willerslev and his colleagues typically ignored. “But now we have started investigating this waste product,” he said.

 

 

The viruses were not trapped alive in the bones. “Just to make it crystal clear, the sequences of viruses that we find are highly fragmented,” said Barbara Mühlemann, a PhD student at the University of Cambridge and the lead author of the study. There is “absolutely no danger,” she said, someone could contract ancient hepatitis by touching a skeleton.

 

Poinar said the technology to perform this work existed for about five years, but it took the right samples to achieve these results. “I think this is the real benefit to ancient DNA,” he said: Scientists can now detect the presence of “key viral genomes at specific points in time” without other physical evidence for a virus's existence. Previously, hunts for ancient viruses often began with the examination of lesions on human remains, as was the case of a 500-year-old pockmarked mummy in Italy found to have hepatitis B.

 

Ancient viral genomes give scientists rough histories of infection. These histories can strengthen hypotheses or discard them, Willerslev pointed out. There had been speculation hepatitis B originated in the New World and spread to Europe about 500 years ago. That idea is “certainly wrong,” he said, given the samples' age.

 

 

"It looks like several of the ancient hepatitis B viruses occurred in different geographical regions than their closest modern relatives," said Alexander Suh, an evolutionary biologist at Uppsala University in Sweden who was not a part of this study. "This provides a glimpse into how the geographic distribution of this disease agent has changed over time."

 

Some versions of the ancient hepatitis virus still infect humans. Another died out. “One of the really cool things is it shows the presence of genotypes that are no longer circulating today — that is, they have gone extinct. We’d expect this,” Poinar said, “but to see it is really neat.”

 

Willerslev said this work is the start of a catalogue of known “possible mutations” for the hepatitis B virus. Ancient strains may or may not appear again, he said, but knowledge of the virus's past adaptations might aid scientists trying predict how hepatitis will mutate in the future.

 

New strains of hepatitis B virus discovered in ancient human remains - The Washington Post  https://www.washingtonpost.com/news/speaking-of-science/wp/2018/05/09/new-strains-of-hepatitis-b-virus-discovered-in-ancient-human-remains/?noredirect=on&utm_term=.1b2ec86f14ee