新冠病毒已突变!
中国科研团队:已产生149个突变点
3月3日, 中国科学院主办的《国家科学评论》发表《关于SARS-CoV-2的起源和持续进化》一文。
论文通讯作者为陆剑研究员(北京大学生命科学学院生物信息中心)、崔杰研究员(中国科学院上海巴斯德研究所)。
研究发现:新冠病毒已产生149个突变点,并演化出了两个亚型,分别是L亚型和S亚型。作者发现S型新冠病毒与蝙蝠来源的冠状病毒在进化树上更接近,从而得出S型相对更古老的结论。
相对古老的S型新冠病毒应该产生更多的病毒株,因其有更多的时间在人群中传播。但基因组数据表明L型占70%,S型占30%,且每个L型病毒株比S型携带了相对较多的新生突变。作者分析了为什么相对年轻的L型新冠病毒却产生了更多的病毒株,推测L型病毒传播能力更强,或者在人体内复制更快,因此可能意味着其毒力也更大。
另外,研究发现绝大多处患者体内提取的病毒株表明其只感染了L型或S型中的一个病毒亚型。L亚型在武汉暴发的早期阶段更为普遍,但由于强力的人为干预,L亚型的发生频率在2020年1月初后有所下降。
值得注意的是,样本显示,大部分患者只感染了L亚型或S亚型中的一个。但其中一位近期有过武汉旅行史的美国患者分离出的病毒株,显示其可能同时感染了L型和S型新冠病毒。不过,作者表示目前还无法排除新突变型的可能性。
人类历史上有很多疾病都源于动物,而确定一种疾病的来源是了解和治疗该种疾病的重要步骤。比如最近深受全世界关注的新型冠状病毒,据研究调查表明,它的宿主就是野生动物,可能是中华菊头蝠。那么,病毒是如何从动物传染到人类的?这期间的感染过程又是怎样的呢?
At a Maryland country fair in 2017, the prize pigs were not looking their best. Farmers reported feverish hogs with inflamed eyes and running snouts. But while fair officials worried about the pigs, the Maryland department of health was concerned about a group of sick fairgoers. Some had pet the pigs, while others had merely been near their barns; but soon, 40 of these attendees would be diagnosed with swine flu. More often than not, sick animals don’t infect humans. But when they do, these cross-species infections, or viral host jumps, have the potential to produce deadly epidemics. So how can pathogens from one species infect another, and what makes host jumps so dangerous?
在马里兰州2017年的郡博览会上,获奖的猪看起来状态并不好。农民报告说,这些发烧的猪眼睛红肿、鼻涕直流。但是,虽然展会官员担心这些猪,但马里兰州卫生部门则对一组生病的参会者很重视。有些人摸过这些猪,而有些人仅从它们的圈旁路过;但很快,这些参与者中40人将被诊断患猪流感。生病动物通常不会感染人类,但是当它们传染时,这些跨物种感染,也叫病毒宿主转移,可能产生致命的流行病。那么一个物种的病原体如何感染另一个物种的?什么使宿主转移如此危险呢?
Viruses are a type of organic parasite infecting nearly all forms of life. To survive and reproduce, they must move through three stages: contact with a susceptible host, infection and replication, and transmission to other inpiduals. As an example, let’s look at human influenza. First, the flu virus encounters a new host and makes its way into their respiratory tract. This isn’t so difficult, but to survive in this new body, the virus must mount a successful infection before it’s caught and broken down by an immune response.
病毒是一种感染几乎所有生命形式的有机寄生物。为了生存和繁殖,它们必须经历三个阶段:与易感宿主接触、感染和复制、以及传递给其他人。举个例子,我们来看看人类流感。首先,流感病毒遇到了新的宿主,并进入他们的呼吸道。进入并不困难,但要在这个新的身体中生存,在病毒被免疫反应捕获并消灭前,它必须成功感染宿主。
To accomplish this task, viruses have evolved specific interactions with their host species. Human flu viruses are covered in proteins adapted to bind with matching receptors on human respiratory cells. Once inside a cell, the virus employs additional adaptations to hijack the host cell’s reproductive machinery and replicate its own genetic material. Now the virus only needs to suppress or evade the host’s immune system long enough to replicate to sufficient levels and infect more cells. At this point, the flu can be passed on to its next victim via any transmission of infected bodily fluid.
要完成这项任务,病毒进化出与宿主物种的特定互动。人流感病毒覆盖着蛋白质,这种蛋白质可以与人类呼吸细胞上的匹配受体结合。一旦进入细胞,病毒就会采用其他适应措施来劫持宿主细胞的分裂机制。并复制自己的基因物质。现在病毒只需压制或躲避宿主的免疫系统,一直繁殖到足够多的水平来感染更多的细胞。此时,流感可通过任何传染性体液传播,并传递给其下一个受害者。
However, this simple sneeze also brings the virus in contact with pets, plants, or even your lunch. Viruses are constantly encountering new species and attempting to infect them. More often than not, this ends in failure. In most cases, the genetic dissimilarity between the two hosts is too great. For a virus adapted to infect humans, a lettuce cell would be a foreign and inhospitable landscape. But there are a staggering number of viruses circulating in the environment, all with the potential to encounter new hosts. And because viruses rapidly reproduce by the millions, they can quickly develop random mutations. Most mutations will have no effect, or even prove detrimental; but a small proportion may enable the pathogen to better infect a new species. The odds of winning this destructive genetic lottery increase over time, or if the new species is closely related to the virus’ usual host. For a virus adapted to another mammal, infecting a human might just take a few lucky mutations. And a virus adapted to chimpanzees, one of our closest genetic relatives, might barely require any changes at all.
然而,简单一个喷嚏还会使病毒与宠物、植物甚至你的午餐接触。病毒不断遇到新物种并试图感染它们,这通常会以失败告终。多数情况下,两个宿主间的遗传基因差异太大,对于已经适应感染人类的病毒,莴苣细胞则是外来的、且不适宜生存的环境。但环境中传播的病毒数量惊人,极有可能遇到新的宿主。而且,因为病毒以数百万级迅速繁殖,他们可以快速发生随机突变。大多数突变都没有效果,甚至证明是有害的;但一小部分变异可使病原体更容易感染新物种。获得这种破坏性基因的几率会随着时间的推移而增加,或者新物种与病毒的常见宿主相似。对于适应一种哺乳动物的病毒,感染人类可能只需一些幸运的突变。一种适应离我们最近的遗传近亲黑猩猩的病毒,几乎不需要任何改变。
It takes more than time and genetic similarity for a host jump to be successful. Some viruses come equipped to easily infect a new host’s cells, but are then unable to evade an immune response. Others might have a difficult time transmitting to new hosts. For example, they might make the host’s blood contagious, but not their saliva. However, once a host jump reaches the transmission stage, the virus becomes much more dangerous. Now gestating within two hosts, the pathogen has twice the odds of mutating into a more successful virus. And each new host increases the potential for a full-blown epidemic.
一个宿主成功转移所需要的不仅仅是时间和基因相似性,有些病毒可以轻易感染新宿主细胞,但是无法逃避免疫反应。其他病毒可能较难传染到新宿主。比如,它们可能使宿主的血液具传染性,而非唾液具有传染性。但是,一旦宿主转移到传播阶段,病毒变得更加危险。现在病原体可在两个宿主中孕育,其变异为成功病毒的概率提高两倍,且每个新的宿主都会增加全面流行病的可能性。
Virologists are constantly looking for mutations that might make viruses such as influenza more likely to jump. However, predicting the next potential epidemic is a major challenge.
病毒学家一直在寻找可能令流感类病毒更易产生宿主转移的突变。然而,预测下一个潜在的流行病是一项重大挑战。
There’s a huge persity of viruses that we’re only just beginning to uncover. Researchers are tirelessly studying the biology of these pathogens. And by monitoring populations to quickly identify new outbreaks, they can develop vaccines and containment protocols to stop these deadly diseases.
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