首次觀察到逃避免疫系統的雜種病毒
研究人員發現呼吸道融合病毒(RSV)和流感病毒融合在一起形成一種新型病毒病原體
資料來源：Linda Geddes / 科學記者 / 2022 年 10 月 24 日 / 衛報 / 財團法人台灣紅絲帶基金會
兩種常見的呼吸道病毒可以融合形成一種能夠逃避人體免疫系統並感染肺細胞的混合病毒——這是有史以來第一次觀察到這種病毒的合作。
研究人員認為，這些發現可能有助於解釋為什麼合併感染會導致某些患者的疾病顯著惡化，包括難以治療的病毒性肺炎。
每年，全球約有 500 萬人因A型流感住院，而呼吸道融合病毒 (respiratory syncytial virus , RSV) 是 5 歲以下兒童急性下呼吸道感染的主要原因，並可能導致部分兒童及較年長之成年人出現嚴重疾病。
雖然合併感染——一個人同時感染兩種病毒——被認為是相對常見的，但目前尚不清楚如果這些病毒發現自己在同一個細胞內，它們會如何反應。
「呼吸道病毒作為許多病毒群落的一部分存在，它們都針對身體的同一區域，就像生態位一樣」，領導這項研究的 MRC-格拉斯哥大學病毒研究中心的喬安妮·哈尼博士說。
「我們需要了解這些感染是如何在彼此的背景下發生的，以便更全面地了解每種病毒的生物學特性」。
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為了進行調查，Haney 和她的同事故意用這兩種病毒感染人類肺細胞，並發現它們並沒有像其他一些已知的病毒那樣相互競爭，而是融合在一起形成一種棕櫚樹狀的雜交病毒——RSV 形成樹幹，流感則為葉子。
「這種混合病毒以前從未被描述過」，監督該研究的 Pablo Murcia 教授說，該研究發表在《自然微生物學》上。「我們談論的是來自兩個完全不同家族的病毒，它們結合了兩種病毒的基因組和外部蛋白質。它是一種新型病毒病原體」。
一旦形成，雜交病毒也能夠感染鄰近的細胞——即使存在通常會阻止感染的流感抗體。儘管抗體仍然粘附在雜交病毒表面的流感蛋白上，但該病毒只是利用鄰近的 RSV 蛋白來感染肺細胞。穆爾西亞說：「流感正在使用混合病毒顆粒作為特洛伊木馬」。
除了幫助病毒逃避免疫系統外，聯合起來還可以使它們接觸到更廣泛的肺細胞。流感通常感染鼻子、喉嚨和氣管中的細胞，而 RSV 往往更喜歡氣管和肺細胞——儘管有一些重疊。
利茲大學的病毒學家斯蒂芬.格里芬博士說，這可能會增加流感引發嚴重甚至致命的肺部感染（稱為病毒性肺炎）的機會。儘管他警告說，需要更多的研究來證明雜交病毒與人類疾病有關。「與季節性流感病毒相比，RSV 更傾向進入肺部深處，而且感染越深入，你就越有可能患上更嚴重的疾病」，他說。
「這是避免感染多種病毒的另一個原因，因為如果我們不採取預防措施保護我們的健康，這種[雜交]可能會發生得更多」。
值得注意的是，該團隊顯示，雜交病毒可以感染培養的細胞層以及單個呼吸細胞。「這很重要，因為細胞以一種真實的方式相互粘連，病毒顆粒必須以正確的方式進出」，格里芬說。
下一步是確認混合病毒是否可以在合併感染的患者中形成，如果可以，又是哪些。「我們需要知道這是否只發生在流感和 RSV 中，或者它是否也擴展到其他病毒組合」，穆爾西亞說。「我的猜測是確實如此。而且，我假設它也延伸到動物[病毒]。這只是我認為將是一段漫長旅程的開始，希望是非常有趣的發現」。
Immune system-evading hybrid virus observed for first time
Researchers found the RSV and influenza viruses fused together to form a new type of virus pathogen
Linda Geddes / Science correspondent/ Mon 24 Oct 2022 / BST / The Guardian
Two common respiratory viruses can fuse to form a hybrid virus capable of evading the human immune system, and infecting lung cells – the first time such viral cooperation has ever been observed.
Researchers believe the findings could help to explain why co-infections can lead to significantly worse disease for some patients, including hard-to-treat viral pneumonia.
Each year, about 5 million people around the world are hospitalised with influenza A, while respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in children under five years old, and can cause severe illness in some children and older adults.
Although co-infections – where a person is infected with both viruses at the same time – are thought to be relatively common, it was unclear how these viruses would respond if they found themselves inside the same cell.
“Respiratory viruses exist as part of a community of many viruses that all target the same region of the body, like an ecological niche,” said Dr Joanne Haney from the MRC-University of Glasgow centre for virus research, who led the study.
“We need to understand how these infections occur within the context of one another to gain a fuller picture of the biology of each individual virus.”
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To investigate, Haney and her colleagues deliberately infected human lung cells with both viruses and found that, rather than competing with one another as some other viruses are known to do, they fused together to form a palm tree-shaped hybrid virus – with RSV forming the trunk, and influenza the leaves.
“This kind of hybrid virus has never been described before,” said Prof Pablo Murcia, who supervised the research, published in Nature Microbiology. “We are talking about viruses from two completely different families combining together with the genomes and the external proteins of both viruses. It is a new type of virus pathogen.”
Once formed, the hybrid virus was also able to infect neighbouring cells – even in the presence of antibodies against influenza that would usually block infection. Although the antibodies still stuck to influenza proteins on the hybrid virus’s surface, the virus merely used neighbouring RSV proteins to infect lung cells instead. Murcia said: “Influenza is using hybrid viral particles as a Trojan horse.”
As well as helping the viruses evade the immune system, joining forces may also enable them to access a wider range of lung cells. Whereas influenza usually infects cells in the nose, throat and windpipe, RSV tends to prefer windpipe and lung cells – although there is some overlap.
Possibly, it could increase the chances of influenza triggering a severe, and sometimes fatal, lung infection called viral pneumonia, said Dr Stephen Griffin, a virologist at the University of Leeds. Although he cautioned that more research was needed to prove that hybrid viruses are implicated in human disease. “RSV tends to go lower down into the lung than the seasonal flu virus, and you’re more likely to get more severe disease the further down the infection goes,” he said.
“It is another reason to avoid getting infected with multiple viruses, because this [hybridisation] is likely to happen all the more if we don’t take precautions to protect our health.”
Significantly, the team showed that the hybrid viruses could infect cultured layers of cells, as well as individual respiratory cells. “This is important because the cells are stuck to one another in an authentic way, and the virus particles will have to go in and out in the right way,” said Griffin.
The next step is to confirm whether hybrid viruses can form in patients with co-infections, and if so, which ones. “We need to know if this happens only with influenza and RSV, or does it extend to other virus combinations as well,” said Murcia. “My guess is that it does. And, I would hypothesise that it extends to animal [viruses] as well. This is just the start of what I think will be a long journey, of hopefully very interesting discoveries.”