為什麼蝙蝠病毒會不斷感染人？

具有里程碑意義的研究揭示了罕見但致命的亨德拉病毒的「溢出」機制。

資料來源：新聞 / 2022 年 11 月 16 日 / 更正 2022 年 11 月 18 日 / 自然 / 財團法人台灣紅絲帶基金會編譯

澳大利亞狐蝠攜帶一種名為亨德拉 (Hendra) 的病毒，該病毒已蔓延到人類並可能導致罕見但致命的呼吸道感染。

圖片來源：Auscape/Universal Images Group/Getty

「嘿伙計們，你能張開你的翅膀給我看看嗎」？佩吉·埃比 (Peggy Eby) 說，她抬頭看著雪梨世紀公園的狐狸棲息地。「我和他們談了很多」。

Eby 是澳大利亞雪梨新南威爾斯大學的野生動物生態學家，他正在尋找哺乳期的雌性和它們剛出生的幼崽，但陰天讓它們依偎在母親的翅膀下。 Eby 研究飛狐（一種蝙蝠）已有大約 25 年的時間。她用雙筒望遠鏡統計了即將給幼崽斷奶的哺乳期雌性蝙蝠的數量——這是蝙蝠是否正在經歷營養壓力的一個指標，因此可能更容易傳播可使人生病的病毒。

每年有數萬人接觸蝙蝠冠狀病毒

澳大利亞狐蝠之所以引起人們的興趣，是因為它們攜帶一種名為亨德拉病毒的病毒，這種病毒會導致一種非常罕見但致命的呼吸道感染，每兩個感染者中就有一個人死亡。與立百 (Nipah) 病毒、SARS-CoV 和 SARS-CoV-2（導致 COVID-19 大流行的病毒）一樣，亨德拉病毒是一種已經傳染給人類的蝙蝠病毒。這些病毒通常透過中間動物傳播給人類，有時會造成致命後果。科學家們知道溢出效應與棲息地喪失有關，但直到現在仍難以確定引發事件的具體條件。

經過詳細調查後，Eby 和她的同事現在可以預測——最多提前兩年——何時可能出現亨德拉病毒外溢。「他們已經確定了溢出效應的環境驅動因素」，馬里蘭州巴爾的摩市約翰霍普金斯大學的傳染病流行病學家 Emily Gurley 說。他們已經確定瞭解如何預防這些事件。結果於 11 月 16 日發表在《自然》雜誌上。

食物壓力

具體來說，研究人員發現，在蝙蝠經歷食物壓力後的幾年裡，亨德拉病毒會發生集群溢出。這些食物短缺通常伴隨著強烈的聖嬰 (El Niño) 現象發生多年，聖嬰現象是熱帶太平洋的一種氣候現象，通常與澳大利亞東部的乾旱有關。但是，如果蝙蝠在冬季賴以生存的樹木在食物短缺的第二年開花，那麼就不會產生溢出效應。不幸的是，問題在於「幾乎沒有任何冬季棲息地」，紐約伊薩卡的康乃爾大學之疾病生態學家和研究合著者 Raina Plowright 說。

英國格拉斯哥大學的獸醫和傳染病生態學家 Sarah Cleaveland 說，這項研究「絕對棒極了」。 「令人興奮的是，它直接導致了解決方案」。克利夫蘭說，這項研究將氣候、環境、營養壓力和蝙蝠生態學的影響結合在一起，可以為研究其他病原體（包括立百病毒和伊波拉病毒）及其病毒家族帶來新的見解。香港大學的保護生物學家 Alice Hughes 說，這項研究「更清楚地了解了這個問題的驅動因素，與其他地方的流行病具有廣泛的相關性」。她說，「該論文強調了我們可能會看到的風險增加」當氣候變化和棲息地喪失的增加時。

城市轉移

亨德拉病毒於 1994 年在澳大利亞布里斯班的一家純種馬訓練機構的馬匹和人類中爆發後被發現。後來的研究證實，病毒從它的蝙蝠宿主——最有可能是黑狐蝠 (Pteropus alecto)——透過糞便、尿液和飛狐在草地上吐出的咀嚼過的果肉傳播給馬。受感染的馬隨後將病毒傳播給人類。感染通常在澳大利亞冬季期間成群發生，在馬群中出現另一群感染之前可能要過幾年，但自 2000 年代初以來病例一直在增加。

蝙蝠洞解開了致命 SARS 病毒之謎——並暗示可能會發生新的爆發

為了研究溢出機制，Plowright、Eby 和他們的同事在澳大利亞東南部約 300,000 平方公里的範圍內收集了此類事件發生的地點和時間、蝙蝠棲息地的位置及其健康、氣候、花蜜短缺和棲息地喪失的數據。 1996 年到 2020 年。然後他們使用模型來確定哪些因素與溢出相關。「我只是對他們擁有的關於生態的無價的數據集感到敬畏」，Gurley說。

在研究過程中，研究小組注意到蝙蝠行為發生了顯著變化。狐蝠從以游牧為主的生活方式——成群結隊地從一個原始森林遷移到另一個森林以尋找花蜜——轉變為在城市和農業地區以小群體形式定居，使蝙蝠更接近馬和人居住的地方。自 2000 年代初以來，被蝙蝠所佔用的棲息地數量總體上增為三倍，到 2020 年達到 320 座左右。

該團隊的另一項研究發現，新建立的棲息地每年冬天都會傳播亨德拉病毒，但在食物短缺後的幾年裡，蝙蝠會傳播更多病毒。位於諾曼的俄克拉荷馬大學專注於傳染病之生態學家亦是研究合著者Daniel Becker 說，「冬季的感染率確實急劇上升」。該研究還將蝙蝠病毒脫落的增加與對馬的溢出效應之增加關聯起來。

尋找花蜜

Plowright 和 Eby 最近發表在《自然》雜誌上的模型顯示，當食物稀缺時，狐蝠種群分裂成小群，遷移到靠近馬匹的農業區，並且在強烈的聖嬰事件之後出現食物短缺，這可能是因為本地桉樹發芽對氣候變化很敏感。為了保存能量，這些年來蝙蝠隻飛行很短的距離，在馬附近的農業區尋找食物。 Plowright 說，對馬的影響最有可能發生在食物短缺後的冬天。他們的模型能夠準確預測這些會在哪幾年發生。

然後意想不到的事情發生了。 2018 年發生聖嬰現象，隨後 2019 年發生乾旱，這顯示 2020 年也應該是一個溢出年。但 5 月份只發生了一起事件，此後沒有發現任何事件。 「我們把所有的卡片都扔回空中，仔細研究了我們假設的所有其他元素」，Eby 說。最終他們發現，當原生森林在食物短缺後的冬季有大量開花活動時，這有助於避免溢出效應。 2020 年，金皮鎮附近的一片紅桉林開花，吸引了大約 240,000 只蝙蝠。 2021年和2022年其他地區也發生了類似的冬季開花事件。

研究人員認為，這些大規模遷徙使蝙蝠遠離了馬匹。 他們建議，透過恢復少數在冬季開花物種的動物棲息地，可以減少對馬的溢出，甚至可能對人類的溢出。 Plowright 說，透過恢復其他攜帶危險病原體動物的棲息地，「也許我們可以預防下一次大流行」。

doi: https://doi.org/10.1038/d41586-022-03682-9

更新和更正：2022 年 11 月 18 日；這個故事的早期版本誤述了 Peggy Eby 在雪梨植物園尋找狐蝠。 她是在世紀公園。

參考文獻：

1. Eby, P. et al. 《 自然 》https://doi.org/10.1038/s41586-022-05506-2 (2022)。

2. Becker, D. J., Eby, P., Madden, W., Peel, A. J. & Plowright, R. K. Ecol. Lett. https://doi.org/10.1111/ele.14007（2022 年）。

Why do bat viruses keep infecting people?

Landmark study reveals ‘spillover’ mechanism for the rare but deadly Hendra virus.

NEWS / 16 November 2022 / Correction 18 November 2022 / Nature

Australian flying foxes host a virus called Hendra, which has spilled over into people and can cause a rare but deadly respiratory infection. Credit: Auscape/Universal Images Group/Getty

“Hey guys, could you open your wings and show me?” says Peggy Eby, looking up at a roost of flying foxes in Sydney’s Centennial Park. “I talk to them a lot.”

Eby, a wildlife ecologist at the University of New South Wales in Sydney, Australia, is looking for lactating females and their newborn pups, but the overcast weather is keeping them snuggled under their mothers’ wings. Eby has been studying flying foxes, a type of bat, for some 25 years. Using her binoculars, she tallies the number of lactating females that are close to weaning their young — a proxy for whether the bats are experiencing nutritional stress and so probably more likely to shed viruses that can make people ill.

Tens of thousands of people exposed to bat coronaviruses each year

Australian flying foxes are of interest because they host a virus called Hendra, which causes a very rare but deadly respiratory infection that kills one in every two infected people. Hendra virus, like Nipah, SARS-CoV and SARS-CoV-2 (the virus that caused the COVID-19 pandemic) is a bat virus that has spilled over into people. These viruses often reach humans through an intermediate animal, sometimes with deadly consequences. Scientists know that spillovers are associated with habitat loss, but have struggled to pinpoint the specific conditions that spark events until now.

After a detailed investigation, Eby and her colleagues can now predict — up to two years ahead — when clusters of Hendra virus spillovers will probably appear. “They have identified the environmental drivers of spillover,” says Emily Gurley, an infectious-diseases epidemiologist at Johns Hopkins University in Baltimore, Maryland. And they have determined how those events could be prevented. The results are published in Nature on 16 November.

Food stress

Specifically, the researchers found that clusters of Hendra virus spillovers occur following years in which the bats experience food stress. And these food shortages typically follow years with a strong El Niño, a climatic phenomenon in the tropical Pacific Ocean that is often associated with drought along eastern Australia. But if the trees the bats rely on for food during the winter have a large flowering event the year after there’s been a food shortage, there are no spillovers. Unfortunately, the problem is that “there’s hardly any winter habitat left”, says Raina Plowright, a disease ecologist and study co-author at Cornell University in Ithaca, New York.

The study is “absolutely fantastic”, says Sarah Cleaveland, a veterinarian and infectious-disease ecologist at the University of Glasgow, UK. “What’s so exciting about it is that it has led directly to solutions.” Cleaveland says the study’s approach of looking at the impact of climate, environment, nutritional stress and bat ecology together could bring new insights to the study of other pathogens, including Nipah and Ebola, and their viral families. The study provides “a much clearer understanding of drivers of this issue, with broad relevance to pandemics elsewhere”, says Alice Hughes, a conservation biologist at the University of Hong Kong. “The paper underscores the enhanced risk we are likely to see” with climate change and increasing habitat loss, she says.

Urban shift

Hendra virus was identified in 1994, following an outbreak in horses and people at a thoroughbred training facility in Brisbane, Australia. Studies later established that the virus spreads from its bat reservoir — most likely the black flying fox (Pteropus alecto) — to horses through faeces, urine and spats of chewed-up pulp the flying foxes spit out on the grass. Infected horses then spread the virus to people. Infections typically occur in clusters during the Australian winter, and several years can go by before another cluster emerges in horses, but cases have been picking up since the early 2000s.

Bat cave solves mystery of deadly SARS virus — and suggests new outbreak could occur

To study the mechanism of spillovers, Plowright, Eby and their colleagues collected data on the location and timing of such events, the location of bat roosts and their health, climate, nectar shortages and habitat loss over some 300,000-square kilometres in southeast Australia from 1996 to 2020. Then they used modelling to determine which factors were associated with spillovers. “I’m just in awe of the invaluable data sets that they have on the ecology,” says Gurley.

Over the course of the study, the team noticed significant changes in the bats’ behaviour. The flying foxes went from having predominantly nomadic lifestyles — moving in large groups from one native forest to the other in search of nectar — to settling in small groups in urban and agricultural areas, bringing the bats closer to where horses and people live. The number of occupied bat roosts in general has trebled since the early 2000s to around 320 in 2020.

A separate study from the team found that the newly established roosts shed Hendra virus every winter, but in years following a food shortage bats shed more virus. There were “really dramatic winter spikes in infection”, says co-author Daniel Becker, an ecologist who focuses on infectious diseases at the University of Oklahoma in Norman. The study also linked increased viral shedding in bats to increased spillovers to horses.

In search of nectar

Modelling in Plowright and Eby’s most recent Nature paper shows that flying-fox populations split into small groups that migrated to agricultural areas close to horses when food was scarce, and that food shortages followed strong El Niño events, probably because native eucalyptus tree budding is sensitive to climate changes. To conserve energy, the bats fly only small distances in these years, scavenging for food in agricultural areas near horses. Spillovers to horses were most likely to occur in winters following a food shortage, says Plowright. Their model was able to accurately predict in which years these would occur.

Then something unexpected happened. An El Niño occurred in 2018 followed by a drought in 2019, suggesting that 2020 should also have been a spillover year. But there was only one event in May and none has been detected since. “We threw all the cards back up into the air and looked carefully at all the other elements of our hypothesis,” says Eby. Eventually they discovered that when native forests have major flowering events in winters following a food shortage, this helps to avert spillovers. In 2020, a red-gum forest near the town of Gympie flowered, drawing in some 240,000 bats. And similar winter flowering events occurred in other regions in 2021 and 2022.

The researchers suggest that these mass migrations take the bats away from horses. They propose that by restoring the habitats of those handful of species that flower in winter, fewer spillovers in horses, and potentially in people, would occur. And by restoring the habitats of other animals that host dangerous pathogens, “maybe we can prevent the next pandemic”, says Plowright.

doi: https://doi.org/10.1038/d41586-022-03682-9

UPDATES & CORRECTIONS

•Correction 18 November 2022: An earlier version of this story misstated that Peggy Eby was looking for flying foxes in Sydney’s Botanic Gardens. She was at Centennial Park.

References

1.Eby, P. et al. Nature https://doi.org/10.1038/s41586-022-05506-2 (2022).

Article Google Scholar 

2.Becker, D. J., Eby, P., Madden, W., Peel, A. J. & Plowright, R. K. Ecol. Lett. https://doi.org/10.1111/ele.14007 (2022).

Article PubMed Google Scholar