By Carl Zimmer Oct. 14, 2021
Coronaviruses discovered in Laotian bats are surprisingly adept at infecting human cells, showing that such deadly features can indeed evolve outside of a lab.
令人感到訝異！在老撾(寮國)之蝙蝠中，被發現的冠狀病毒擅長於感染人類細胞。顯示，在實驗室外面，這種致命的特質確實能進行演化。
圖1. 一種很小的馬蹄蝙蝠(Rhinolophus pusillus)是該研究中，被觀察的三種馬蹄蝙蝠之一。 (圖援用自原文)
In the summer of 2020, half a year into the coronavirus pandemic, scientists traveled into the forests of northern Laos to catch bats that might harbor close cousins of the pathogen.
於2020年夏天，冠狀病毒大流行病半年後，科學家們前往老撾北部森林，捕捉可能是該病原體近親的蝙蝠。
In the dead of night, they used mist nets and canvas traps to snag the animals as they emerged from nearby caves, gathered samples of saliva, urine and feces, then released them back into the darkness.
在夜深人靜時，他們用霧狀網及帆布陷阱，來纏住從附近洞穴出來的此些動物，以收集唾液、尿液及糞便樣本，然後釋放它們回黑暗中。
The fecal samples turned out to contain coronaviruses, which the scientists studied in high security biosafety labs, known as BSL-3, using specialized protective gear and air filters.
在被稱為BSL-3之高度安全的生物安全實驗室中，此些科學家使用專門的防護裝備及空氣過濾器，進行研究。結果證實，此些糞便樣本具有冠狀病毒。
Three of the Laos coronaviruses were unusual: They carried a molecular hook on their surface that was very similar to the hook on the virus that causes Covid-19, called SARS-CoV-2. Like SARS-CoV-2, their hook allowed them to latch onto human cells.
有三種老撾的蝙蝠冠狀病毒很不尋常：在它們的表面具有一種，極類似在引發2019冠狀病毒症(COVID-19：Coronavirus Disease-19)，被稱為第二型嚴重急性呼吸系統徵候群-冠狀病毒(SARS-CoV-2：Severe Acute Respiratory Syndrome Coronavirus-2)的病毒上，使此些病毒得以緊抓住人類細胞的分子鉤子。
“It is even better than early strains of SARS-CoV-2,” said Marc Eloit, a virologist at the Pasteur Institute in Paris who led the study, referring to how well the hook on the Laos coronaviruses binds to human cells. The study was posted online last month and has not yet been published in a scientific journal.
於法巴黎巴斯德研究所，領導該項研究的病毒學家，Marc Eloit宣稱：「這種鉤子甚至比早期的SARS-CoV-2病毒株更佳。」是指老撾之蝙蝠冠狀病毒上的鉤子與人類細胞結合有多完全。該項研究上個月被張貼於網路上，不過尚未發表於科學期刊。
Virus experts are buzzing about the discovery. Some suspect that these SARS-CoV-2-like viruses may already be infecting people from time to time, causing only mild and limited outbreaks. But under the right circumstances, the pathogens could give rise to a Covid-19-like pandemic, they say.
有關此發現，病毒專家們議論紛紛。有些人懷疑，此些類似SARS-CoV-2的病毒，可能已經不時地感染人類，僅引起輕微且有限的爆發。他們表示，不過在適當環境下，此種病原體可能引發類似Covid-19的大流行病。
The findings also have significant implications for the charged debate over Covid’s origins, experts say. Some people have speculated that SARS-CoV-2’s impressive ability to infect human cells could not have evolved through a natural spillover from an animal. But the new findings seem to suggest otherwise.
專家們表示，此些研究發現也具有，關於Covid起源可能引起激烈爭議的諸多重大密切關係。有些人一直推測，SARS-CoV-2令人印象深刻之感染人類細胞的能力，不可能已經從動物，透過一種自然外溢，進行了演化。不過，此些新發現似乎顯示並非那樣。
“That really puts to bed any notion that this virus had to have been concocted, or somehow manipulated in a lab, to be so good at infecting humans,” said Michael Worobey, a University of Arizona virologist who was not involved in the work.
美國亞利桑那大學未涉及該項研究的病毒學家，Michael Worobey宣稱：「那確實鋪陳了，此種病毒必須被調製，或在實驗室中，以某種方式被操縱，才能如此善於感染人類的任何見解。」
These bat viruses, along with more than a dozen others discovered in recent months in Laos, Cambodia, China and Thailand, may also help researchers better anticipate future pandemics. The viruses’ family trees offer hints about where potentially dangerous strains are lurking, and which animals scientists should look at to find them.
這些蝙蝠病毒及最近幾個月，在老撾、柬埔寨、中國與泰國發現的十多種其他病毒，也可能有助於研究人員們，更佳地預測未來的大流行病。此些病毒的家譜提供了，有關潛在危險病毒株潛伏在哪裡的線索，及科學家們應該探究哪些動物，以找到它們。
Three bats captured in northern Laos carried viruses that were remarkably similar to SARS-CoV-2, the virus that causes Covid-19. Samples from wild animals, below, may help researchers anticipate future pandemics.
在老撾北部捕獲的三隻蝙蝠具有顯著類似，引發Covid-19之SARS-CoV-2 的病毒。來自野生動物的樣本(請參閱原文：https://www.nytimes.com/2021/10/14/science/bat-coronaviruses-lab-leak.html)，可能有助於研究人員們，預測未來的大流行病。
Last week, the U.S. government announced a $125 million project to identify thousands of wild viruses in Asia, Latin America and Africa to determine their risk of spillover. Dr. Eloit predicted that there were many more relatives of SARS-CoV-2 left to find.
上星期，美國政府宣布了一項1.25億美元的計劃，旨在識別亞洲、拉丁美洲及非洲的數千種野生病毒，以確定其外溢風險。Eloit博士預測，有更多SARS-CoV-2的親緣病毒待發現。
“I am a fly fisherman,” he said. “When I am unable to catch a trout, that doesn’t mean there are no trout in the river.”
他宣稱：「他是名用假蠅的釣魚者。當他釣不到鱒魚時，那並不意味著河裡沒有鱒魚。」
When SARS-CoV-2 first came to light, its closest known relative was a bat coronavirus that Chinese researchers found in 2016 in a mine in southern China’s Yunnan Province. RaTG13, as it is known, shares 96 percent of its genome with SARS-CoV-2. Based on the mutations carried by each virus, scientists have estimated that RaTG13 and SARS-CoV-2 share a common ancestor that infected bats about 40 years ago.
當SARS-CoV-2首度曝光時，其已知的最近親是，2016年中國研究人員們，於中國南部雲南省，一處礦坑發現的一種蝙蝠冠狀病毒─RaTG13。眾所周知，其基因體與SARS-CoV-2共享96%。根據每一病毒具有的突變，科學家們估算RaTG13及SARS-CoV-2共有一個，大約40年前，感染了蝙蝠的共同祖先。
Both viruses infect cells by using a molecular hook, called the “receptor-binding domain,” to latch on to their surface. RaTG13’s hook, adapted for attaching to bat cells, can only cling weakly to human cells. SARS-CoV-2’s hook, by contrast, can clasp cells in the human airway, the first step toward a potentially lethal case of Covid-19.
這兩種病毒都藉由使用，被稱為“受體結合域”的分子鉤子，抓牢細胞表面，來感染細胞。RaTG13適合附著於蝙蝠細胞上的鉤子，僅能微弱地抓住人類細胞。相較之下，SARS-CoV-2的鉤子能鉤住人類呼吸道中的細胞，這是邁向可能致命之Covid-19病例的第一步。
To find other close relatives of SARS-CoV-2, wildlife virus experts checked their freezers full of old samples from across the world. They identified several similar coronaviruses from southern China, Cambodia, and Thailand. Most came from bats, while a few came from scaly mammals known as pangolins. None was a closer relative than RaTG13.
為了找尋SARS-CoV-2的其他近親，野生動物病毒專家們檢查了，他們裝滿來自世界各地之舊樣本的冰箱。從來自中國南部、柬埔寨及泰國的病毒中，他們確認了幾種類似的冠狀病毒。大多數來自蝙蝠，不過少數來自被通稱為穿山甲的有鱗哺乳動物。無一比RaTG13更為近親。
Dr. Eloit and his colleagues instead set out to find new coronaviruses.
They traveled to northern Laos, about 150 miles from the mine where Chinese researchers had found RaTG13. Over six months they caught 645 bats, belonging to 45 different species. The bats harbored two dozen kinds of coronaviruses, three of which were strikingly similar to SARS-CoV-2 — especially in the receptor-binding domain.
因此，Eloit博士及其同僚們著手，尋找新的冠狀病毒。他們前往距離中國研究人員們發現RaTG13的礦坑，大約150英里的老撾北部。在六個月期間，他們捕獲了645隻，屬於45個不同物種的蝙蝠。此些蝙蝠窩藏了20多種冠狀病毒，其中三種顯著與SARS-CoV-2相似。特別是，在受體結合域部分。
In RaTG13, 11 of the 17 key building blocks of the domain are identical to those of SARS-CoV-2. But in the three viruses from Laos, as many as 16 were identical — the closest match to date.
在RaTG13中，該結合域的17個關鍵構材中，11個完全與SARS-CoV-2相同。不過，在來自老撾的三種病毒中，多達16種是完全相同的。這是迄今最接近的相似病毒。
Dr. Eloit speculated that one or more of the coronaviruses might be able to infect humans and cause mild disease. In a separate study, he and colleagues took blood samples from people in Laos who collect bat guano for a living. Although the Laotians did not show signs of having been infected with SARS-CoV-2, they carried immune markers, called antibodies, that appeared to be caused by a similar virus.
Eloit博士推測，這些冠狀病毒的一或多種，或許能感染人類並引發輕微疾病。在一項獨立研究中，他及同僚們從收集蝙蝠糞為生的老撾人，採集了血液樣本。雖然此些老撾人沒有顯現，曾被SARS-CoV-2感染的跡象，不過他們具有，似乎由類似病毒所引起，被稱為抗體的免疫標記。
Linfa Wang, a molecular virologist at the Duke-NUS Medical School in Singapore who was not involved in the study, agreed that such an infection was possible, since the newly discovered viruses can attach tightly to a protein on human cells called ACE2.
新加坡杜克-新加坡國立大學醫學院，未涉及這項研究的分子病毒學家，Linfa Wang認同這種感染是可能的。因為，此些新近發現的病毒，能緊密附著於人類細胞，被稱為ACE2的一種蛋白質上。
“If the receptor binding domain is ready to use ACE2, these guys are dangerous,” Dr. Wang said.
Wang博士宣稱：「倘若受體結合域準備好利用ACE2，則這些是危險的傢伙。」
Paradoxically, some other genes in the three Laotian viruses are more distantly related to SARS-CoV-2 than other bat viruses. The cause of this genetic patchwork is the complex evolution of coronaviruses.
矛盾的是，在這三種老撾之病毒中的其他一些基因，與SARS-CoV-2的親緣關係，比其他蝙蝠病毒更疏遠。此遺傳雜集的原因，是冠狀病毒的複雜演化。
If a bat infected with one coronavirus catches a second one, the two different viruses may end up in a single cell at once. As that cell begins to replicate each of those viruses, their genes get shuffled together, producing new virus hybrids.
倘若一隻感染了一種冠狀病毒的蝙蝠，又感染上第二種冠狀病毒，這兩種不同病毒可能同時進入單一細胞中。當此細胞開始複製那些病毒中的每一種時，它們的基因被改組在一起，而產生新的混種病毒。
In the Laotian coronaviruses, this gene shuffling has given them a receptor-binding domain that’s very similar to that of SARS-CoV-2. The original genetic swap took place about a decade ago, according to a preliminary analysis by Spyros Lytras, a graduate student at the University of Glasgow in Scotland.
在此些老撾的冠狀病毒中，這種基因改組已經賦予它們一種，非常類似SARS-CoV-2那種的受體結合域。根據蘇格蘭格拉斯哥大學，研究生Spyros Lytras的初步分析，最初的基因交換發生於，大約十年前。
Mr. Lytras and his colleagues are now comparing SARS-CoV-2 not just to the new viruses from Laos, but to other close relatives that have been found in recent months. They’re finding even more evidence of gene shuffling. This process — known as recombination — may be reshaping the viruses from year to year.
目前，Lytras先生及其同僚們不只正在進行，SARS-CoV-2與來自老撾之新病毒的比較，而且進行與最近幾個月已經被發現之其他近親病毒的比較。他們發現了更多基因改組的證據。該被通稱為重組的過程，可能年復一年地重新塑造此些病毒。
“It’s becoming more and more obvious how important recombination is,” Mr. Lytras said.
Lytras先生宣稱：「重組的重要性，正變得越來越顯著。」
He and his colleagues are now drawing the messy evolutionary trees of SARS-CoV-2-like viruses based on these new insights. Finding more viruses could help clear up the picture. But scientists are divided as to where to look for them.
目前，他及其同僚們正根據此些新見解，來繪製類似SARS-CoV-2病毒的紊亂演化樹。發現更多病毒可能有助於澄清問題。不過，科學家們對於何處尋找它們，是分歧的。
Dr. Eloit believes the best bet is a zone of Southeast Asia that includes the site where his colleagues found their coronaviruses, as well as the nearby mine in Yunnan where RaTG13 was found.
Eloit博士認為，除了在雲南發現RaTG13的附近礦坑之外，最佳的選擇是包括，他的同僚們發現其冠狀病毒之所在地的東南亞地區。
“I think the main landscape corresponds to north Vietnam, north Laos and south China,” Dr. Eloit said.
Eloit博士宣稱：「他認為，主要地帶相當於越南北部、老撾北部及中國南部。」
The U.S. government’s new virus-hunting project, called DEEP VZN, may turn up one or more SARS-CoV-2-like viruses in that region. A spokesman for USAID, the agency funding the effort, named Vietnam as one of the countries where researchers will be searching, and said that new coronaviruses are one of their top priorities.
美國政府名為 DEEP VZN(Viral Zoonoses：病毒性人畜共通病)的新病毒搜尋計劃，在那區域，可能找到一或多種類似SARS-CoV-2的病毒。資助該項研究之機構，美國國際開發署(USAID：United States Agency for International Development)的發言人，指名越南為研究人員們將進行搜尋的國家之一。且表示，新型冠狀病毒是他們居首的重點之一。
Other scientists think it’s worth looking for relatives of SARS-CoV-2 further afield. Dr. Worobey of the University of Arizona said that some bat coronaviruses carrying SARS-CoV-2-like segments have been found in eastern China and Thailand.
其他的科學家認為，值得進一步廣泛地尋找SARS-CoV-2的同類病毒。美國亞利桑那大學Worobey博士表示，在中國東部及泰國已經被發現的一些蝙蝠冠狀病毒，具有類似SARS-CoV-2的基因片段。
“Clearly the recombination is showing us that these viruses are part of a single gene pool over hundreds and hundreds of miles, if not thousands of miles,” Dr. Worobey said.
Worobey宣稱：「顯然，上述重組為咱我們展示了，這些病毒倘若不是在數千英里，至少也是數百英里範圍之單個基因庫的一部分。」
Colin Carlson, a biologist at Georgetown University, suspects that a virus capable of producing a Covid-like outbreak might be lurking even further away. Bats as far east as Indonesia and as far west as India, he noted, share many biological features with the animals known to carry SARS-CoV-2-like viruses.
美國喬治城大學(位於首都華盛頓特區)的生物學家，Colin Carlson懷疑，一種能引起類似Covid爆發的病毒，可能潛藏於更遠的地方。他特別指出，東遠至印度尼西亞，西遠至印度的蝙蝠，與已知具有類似SARS-CoV-2病毒的動物，共有諸多生物特徵。
“This is not just a Southeast Asia problem,” Dr. Carlson said. “These viruses are diverse, and they are more cosmopolitan than we have thought.”
Carlson博士宣稱：「這不只是東南亞的問題。此些病毒是多種多樣的，而且比人們曾想像的更為遍生。」
The interest in the origins of the pandemic has put renewed attention on the safety measures researchers are using when studying potentially dangerous viruses. To win DEEP VZN grants, scientists will have to provide a biosafety and biosecurity plan, according to a USAID spokesman, including training for staff, guidelines on protective equipment to be worn in the field and safety measures for lab work.
對大流行病起源的關注，已經使研究人員們，在研究具有潛在危險的病毒時，重新關注使用的安全措施。據美國國際開發署發言人的說法，為了贏得DEEP VZN的資助，科學家們將必須提供一項，包括員工培訓、於現場穿戴防護設備指南及實驗室工作安全措施的生物安全暨生物保護措施計劃。
If scientists find more close cousins of SARS-CoV-2, it doesn’t necessarily mean they pose a deadly threat. They might fail to spread in humans or, as some scientists speculate, cause only small outbreaks. Just seven coronaviruses are known to have jumped the species barrier to become well-established human pathogens.
倘若科學家們發現SARS-CoV-2的更近親病毒，未必意味著它們構成致命威脅。它們可能無法在人類中傳播，或像一些科學家推測的那樣，只會引起小規模爆發。已知僅七種冠狀病毒已經跨越物種障礙，成為被確認的人類病原體。
“There’s probably a vast range of other coronaviruses that end up going nowhere,” said Jessica Metcalf, an evolutionary ecologist at Princeton University.
Still, recombination may be able to turn a virus going nowhere into a new threat. In May, researchers reported that two coronaviruses in dogs recombined in Malaysia. The result was a hybrid that infected eight children.
美國普林斯頓大學演化生態學家，Jessica Metcalf宣稱：「可能有大量的其他冠狀病毒，最終一無所成。」儘管如此，重組或許能將一無所成的病毒，轉變成一種新威脅。在2021年5月，研究人員們報告說，在馬來西亞，兩種冠狀病毒於狗體內重組。結果是一種，感染了八個孩子的混種。
“When a coronavirus that we have monitored for decades, that we think of as just something our pets can get, can make the jump — we should have seen that coming, right?” Dr. Carlson said.
Carlson博士宣稱：「當已經被密切注意幾十年，人們認為只是咱們寵物會得到之事的冠狀病毒，會產生上述躍變。我們應該已經看到那的降臨，不是嗎？」
網址：https://www.nytimes.com/2021/10/14/science/bat-coronaviruses-lab-leak.html
翻譯：許東榮
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