新冠病毒已突變！
中國科研團隊：已產生149個突變點
3月3日， 中國科學院主辦的《國家科學評論》發表《關于SARS-CoV-2的起源和持續進化》一文。
論文通訊作者為陸劍研究員（北京大學生命科學學院生物信息中心）、崔杰研究員（中國科學院上海巴斯德研究所）。
研究發現：新冠病毒已產生149個突變點，并演化出了兩個亞型，分別是L亞型和S亞型。作者發現S型新冠病毒與蝙蝠來源的冠狀病毒在進化樹上更接近，從而得出S型相對更古老的結論。
相對古老的S型新冠病毒應該產生更多的病毒株，因其有更多的時間在人群中傳播。但基因組數據表明L型占70%，S型占30%，且每個L型病毒株比S型攜帶了相對較多的新生突變。作者分析了為什么相對年輕的L型新冠病毒卻產生了更多的病毒株，推測L型病毒傳播能力更強，或者在人體內復制更快，因此可能意味著其毒力也更大。
另外，研究發現絕大多處患者體內提取的病毒株表明其只感染了L型或S型中的一個病毒亞型。L亞型在武漢暴發的早期階段更為普遍，但由于強力的人為干預，L亞型的發生頻率在2020年1月初后有所下降。
值得注意的是，樣本顯示，大部分患者只感染了L亞型或S亞型中的一個。但其中一位近期有過武漢旅行史的美國患者分離出的病毒株，顯示其可能同時感染了L型和S型新冠病毒。不過，作者表示目前還無法排除新突變型的可能性。
人類歷史上有很多疾病都源于動物，而確定一種疾病的來源是了解和治療該種疾病的重要步驟。比如最近深受全世界關注的新型冠狀病毒，據研究調查表明，它的宿主就是野生動物，可能是中華菊頭蝠。那么，病毒是如何從動物傳染到人類的？這期間的感染過程又是怎樣的呢？
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?
在馬里蘭州2017年的郡博覽會上，獲獎的豬看起來狀態并不好。農民報告說，這些發燒的豬眼睛紅腫、鼻涕直流。但是，雖然展會官員擔心這些豬，但馬里蘭州衛生部門則對一組生病的參會者很重視。有些人摸過這些豬，而有些人僅從它們的圈旁路過;但很快，這些參與者中40人將被診斷患豬流感。生病動物通常不會感染人類，但是當它們傳染時，這些跨物種感染，也叫病毒宿主轉移，可能產生致命的流行病。那么一個物種的病原體如何感染另一個物種的？什么使宿主轉移如此危險呢？
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.
病毒是一種感染幾乎所有生命形式的有機寄生物。為了生存和繁殖，它們必須經歷三個階段：與易感宿主接觸、感染和復制、以及傳遞給其他人。舉個例子，我們來看看人類流感。首先，流感病毒遇到了新的宿主，并進入他們的呼吸道。進入并不困難，但要在這個新的身體中生存，在病毒被免疫反應捕獲并消滅前，它必須成功感染宿主。
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.
要完成這項任務，病毒進化出與宿主物種的特定互動。人流感病毒覆蓋著蛋白質，這種蛋白質可以與人類呼吸細胞上的匹配受體結合。一旦進入細胞，病毒就會采用其他適應措施來劫持宿主細胞的分裂機制。并復制自己的基因物質。現在病毒只需壓制或躲避宿主的免疫系統，一直繁殖到足夠多的水平來感染更多的細胞。此時，流感可通過任何傳染性體液傳播，并傳遞給其下一個受害者。
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，簡單一個噴嚏還會使病毒與寵物、植物甚至你的午餐接觸。病毒不斷遇到新物種并試圖感染它們，這通常會以失敗告終。多數情況下，兩個宿主間的遺傳基因差異太大，對于已經適應感染人類的病毒，萵苣細胞則是外來的、且不適宜生存的環境。但環境中傳播的病毒數量驚人，極有可能遇到新的宿主。而且，因為病毒以數百萬級迅速繁殖，他們可以快速發生隨機突變。大多數突變都沒有效果，甚至證明是有害的;但一小部分變異可使病原體更容易感染新物種。獲得這種破壞性基因的幾率會隨著時間的推移而增加，或者新物種與病毒的常見宿主相似。對于適應一種哺乳動物的病毒，感染人類可能只需一些幸運的突變。一種適應離我們最近的遺傳近親黑猩猩的病毒，幾乎不需要任何改變。
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.
一個宿主成功轉移所需要的不僅僅是時間和基因相似性，有些病毒可以輕易感染新宿主細胞，但是無法逃避免疫反應。其他病毒可能較難傳染到新宿主。比如，它們可能使宿主的血液具傳染性，而非唾液具有傳染性。但是，一旦宿主轉移到傳播階段，病毒變得更加危險。現在病原體可在兩個宿主中孕育，其變異為成功病毒的概率提高兩倍，且每個新的宿主都會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.
病毒學家一直在尋找可能令流感類病毒更易產生宿主轉移的突變。然而，預測下一個潛在的流行病是一項重大挑戰。
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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