病毒之间如何相互抑制 - 龙腾网移动版

This winter's "tripledemic" is one of several recent odd trends among respiratory virus infections. Viruses, it turns out, can block one another and take turns to dominate.

今年冬季的“三重流行病”是最近出现的呼吸道病毒感染异常趋势之一。事实证明，病毒能够相互抑制，交替占据主流。

Three years into the pandemic, Covid-19 is still going strong, causing wave after wave as case numbers soar, subside, then ascend again. But this past autumn saw something new – or rather, something old: the return of the flu. Plus, respiratory syncytial virus (RSV) – a virus that makes few headlines in normal years – ignited in its own surge, creating a "tripledemic".

大流行爆发三年后，新冠病毒仍在蔓延，随着病例数量的攀升、下降、再攀升，引发了一波又一波疫情。但去年秋季出现了新病毒，更确切地说是老病毒：流感卷土重来。另外，呼吸道合胞病毒——平时很少成为头条新闻——感染人数攀升，形成了“三重流行病”。

The surges in these old foes were particularly striking because flu and RSV all but disappeared during the first two winters of the pandemic. Even more surprising, one particular version of the flu may have gone extinct during the early Covid-19 pandemic. The World Health Organization's surveillance programme has not definitively detected the B/Yamagata flu strain since March 2020.

这些老对手的病例激增尤为惊人，因为在大流行的头两年冬天，流感和呼吸道合胞病毒几乎消失了。更惊人的是，有一种特殊的流感毒株可能在新冠大流行初期绝迹了。自2020年3月以来，世界卫生组织的监测计划尚未明确发现乙型Yamagata系流感毒株。

"I don't think anyone is going to stick their neck out and say it's gone just yet," says Richard Webby, a virologist at St Jude Children's Research Hospital in Memphis. But, he adds, "we hope it got squeezed out." Such an extinction would be a super rare event, Webby says.

“我想没人敢冒险说它已经消失了”，孟菲斯圣犹达儿童研究医院的病毒学家理查德·威比说道。但是，他补充道：“我们希望它被挤走了”。这种灭绝是极其罕见的事件，威比说道。

But then, the past few years have been highly unusual times for human-virus relations, and lockdowns and masks went a long way toward preventing flu and RSV from infiltrating human nostrils. Still, Webby thinks another factor may have kept them at bay while Covid-19 raged. It's called viral interference, and it simply means that the presence of one virus can block another.

但在人类与病毒的关系方面，过去几年是极不寻常的时期。封城和口罩对于预防流感和呼吸道合胞病毒渗入鼻孔有大有帮助。但威比认为在新冠病毒蔓延期间，另一个因素可能抑制了它们。这被称为病毒干扰，是指一种病毒抑制另一种病毒。

Viral interference can happen in individual cells in the laboratory, and in individual animals and people exposed to multiple viruses – but it can also play out across entire populations, if enough people get one virus for it to hinder the flourishing of others at scale. This results in waves of infections by individual viruses that take turns to dominate. "Looking back over the past couple of years, I'm pretty confident in saying that Covid can certainly block flu and RSV," Webby says.

病毒干扰可发生在实验室里的单个细胞中，或者接触多种病毒的单个动物和人的体内——但如果足够多的人感染某种病毒，由它抑制其他病毒的大规模蔓延，那么全体人口也会发生病毒干扰。“回顾过去几年的情况，我确信新冠病毒肯定抑制了流感病毒和呼吸道合胞病毒”，威比说道。
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It may be a while before we can be sure, but it looks likely that Covid-19 could block flu and RSV

我们可能暂时还不确定，但新冠病毒似乎能够抑制流感和呼吸道合胞病毒。

It wouldn't be the first time that scientists have observed such patterns. Back in 2009, for example, the virus to fear was swine flu, which had jumped from pigs to people in spring of that year. It looked poised to ramp up as autumn arrived – but suddenly, in some parts of Europe, it stagnated. The rhinovirus, responsible for the common cold and likely spread by children returning to school, took centre stage for a series of weeks before swine flu recaptured dominance. That flu strain then delayed the typical autumn rise of RSV by as much as two and a half months.

科学家已经不是第一次观察到这种现象了。例如2009年春天，猪流感传染给人类而引起恐慌，看上去势必会在秋季爆发，但突然在欧洲部分地区停止了传播。引起感冒并可能由儿童传播的鼻病毒重返校园，连续几周占据主流后，猪流感才再次占据主流。这种流感毒株将通常在秋天爆发的呼吸道合胞病毒延缓了两个半月。

Running interference

连续干扰

There are a number of ways that interference can happen in the body. One occurs when two viruses use the same molecule to gain entry into host cells. If virus A gets there first, and grabs on to all those molecular doorknobs, then virus B will have no opportunity to enter.

人体内会发生多种干扰方式。一种是当两种病毒利用同一分子进入宿主细胞时，如果病毒A捷足先登，霸占了所有的分子门把手，病毒B就没机会进入了。

Another kind of interference might happen if two viruses compete for the same resources inside the cell, such as the machinery to make new viral proteins or the means to escape that cell to infect others. "Think of it as a race between two viruses," Webby says.

当两种病毒竞争细胞内的同一资源时可能发生干扰，例如制造新病毒蛋白的机制，或者逃逸后感染其他细胞的手段。“可以看成两种病毒的竞争”，威比说道。

But the best-understood method of interference concerns a defensive molecule called interferon that's made by cells of all animals with backbones (and possibly some invertebrates too). Indeed, viral interference is the reason interferon got its name to begin with. When a cell senses a virus, any virus, it starts making interferon. And that, in turn, activates a slew of defensive genes. Some of the products of those genes work inside the cell or at its boundaries, where they prevent additional viruses from entering and block viruses already present from replicating or exiting the cell.

但是，最为人所知的干扰方式是所有的脊椎动物（可能还有某些无脊椎动物）的细胞分泌一种名为干扰素的防御分子。事实上，干扰素正是因为病毒干扰而得名，细胞在感知到病毒时开始分泌干扰素，而干扰素会激活大量的防御基因。这些基因的某些产物在细胞内部或边缘发挥作用，阻止更多的病毒进入细胞，并抑制细胞内现有病毒的复制或逃逸。
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Cells secrete interferon into their surroundings, warning other cells to put up their guard. The result of all this: If a second virus then comes along, cells have their defences already activated, and they may be able to shut it out.

细胞向周围分泌干扰素，警告其他细胞筑起防线。结果是这样的：如果第二种病毒入侵，此时细胞已经激活防御机制，有可能将它们拒之门外。

This "beware" message can spread throughout the body. So, in theory, getting a respiratory virus such as the rhinovirus could activate defences in, say, the gut, protecting the same person from an entirely different virus, such as norovirus. But the situation will vary depending on the viruses involved, the amount of interferon produced, and other factors. "Most of the viruses themselves have ways to neutralise the interferon system," says Ganes Sen, a virologist at the Cleveland Clinic in Ohio, who wrote about the interactions between interferon and viruses for the Annual Review of Virology in 2015. "It's a tug of war."

“警报”信息可传遍整个身体。所以从理论上，感染一种呼吸道病毒（例如鼻病毒）能激活内脏的防御机制，防止这个人感染另一种截然不同的病毒，例如诺如病毒。但具体情况取决于病毒的种类、分泌干扰素的多少以及其他因素。“大多数病毒有办法破坏干扰素系统”，俄亥俄州克利夫兰医学中心的病毒学家加内·森说道。2015年，他曾在《病毒学年鉴》上发表过关于干扰素与病毒之间相互作用的文章。“这是一场拉锯战”。

Scientists study that back-and-forth in animals and other systems in the laboratory. For example, Ellen Foxman, an immunologist at Yale School of Medicine, investigates viral interactions in lab-grown tissues made from real human airway cells. In one experiment, she studied swine flu and a typical representative of the rhinovirus family. When Foxman and her co-authors Anchi Wu, Valia Mihaylova and Marie Landry infected the human tissue first with the rhinovirus, and then with swine flu, interferon prevented the flu from getting a foothold. In similar studies, Foxman found that rhinovirus infection also interfered with subsequent Sars-CoV-2 infection (the virus that causes Covid-19).

科学家们在实验室里反复研究了动物和其他系统内的相互作用。例如，耶鲁医学院的免疫学家埃伦·福克斯曼研究了实验室培育的组织中发生的病毒相互作用，该组织是利用真实的人类支气管细胞培育而成。她在一次试验中研究了猪流感和一种典型的鼻病毒，福克斯曼与她的合著者吴安琪、瓦利亚·米哈洛娃、玛利·兰德里先让人类组织感染了鼻病毒，然后感染猪流感，结果干扰素阻止了猪流感站稳脚跟。在类似的研究中，福克斯曼发现感染鼻病毒也会干扰随后感染的SARS-CoV-2病毒（导致2019冠状病毒病）。

While some viruses can block others, it is still possible to get two viruses at once

虽然某些病毒能抑制其他病毒，但仍有可能同时受到两种病毒的感染。

It's not always reliable to extrapolate from tissues in the laboratory to people or populations, but Foxman thinks the studies reflect biological truth. "It's probable that if you get a rhinovirus infection, that's going to make you relatively resistant to another virus for some period of time," she says. Foxman speculates that the protective effect probably lasts days or weeks.

根据实验室里的组织去推断人或人群未必可靠，但福克斯曼认为这些研究反映出一个生物真相。“如果你感染了鼻病毒，它可能使你在一段时期内相对免疫另一种病毒”，她说道。福克斯曼推测，这种保护效应可能持续数天或数周。

But don't go counting on a cold granting you temporary immunity from other viruses. Interference isn't guaranteed. It's certainly possible to catch more than one virus at the same time. And interferon isn't always beneficial, either – sometimes, it can make people more susceptible to infection, not less. A well-known example is that the flu makes people more susceptible to a secondary bacterial infection.

但是，不要指望感冒让你暂时免疫其他病毒。干扰未必发生，同时感染一种以上病毒是有可能的。干扰素并不总是有益的，有时使人更容易感染病毒。众所周知的例子是，流感使人更容易感染第二种病毒。

In the ongoing pandemic, it's still hard to say how much of a role, if any, interference played in shutting down RSV and flu in populations around the globe. During the first Covid wave in 2020, Foxman thinks that not enough people had Covid for it to be interfering with other viruses on a grand scale. (RSV underwent an unusual summer peak in 2021 as people eased up on masking and other precautions.)

在持续不断的大流行中，尚不确定干扰在阻断全球人口感染呼吸道合胞病毒和流感中起了多大作用（如果起作用的话）。福克斯曼认为，在2020爆发的第一波新冠疫情中，感染新冠病毒的人数不足以大规模干扰其他病毒（2021年夏季出现了异常的呼吸道合胞病毒感染高峰，因为人们放松了佩戴口罩和其他预防措施）。

But by the second Covid winter, in 2021-22, Webby thinks he sees population-level evidence for interference. Influenza was starting to pick up in the fall, he says, but then the omicron variant of Covid burst onto the scene. Flu rates fell – even though people were back at work and school and traveling for the holidays. The coronavirus had a big advantage that season, he says, because many people still lacked immunity to it. It doesn't mean Covid will always edge out influenza in the future.

但是，在2021-22年爆发的第二波冬季新冠疫情中，威比认为自己发现了干扰在起效的群体证据。流感在秋天进入高峰期，他说道，但后来奥密克戎毒株突然爆发。流感发病率下降，尽管人们恢复了工作、学习、假日旅行。新冠病毒在那个季节有很大优势，他说道，因为许多人仍然对它缺少免疫力。这并不意味着新冠病毒在将来总能战胜流感。
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In the third Covid winter now underway in the Northern Hemisphere, conditions are different yet again. Many people now have immunity to Covid, from a recent bout or from vaccination, but fewer have experienced RSV or flu in recent memory. That set the scene for flu and RSV to stage a massive dual comeback, hitting early and hard.

现在北半球已进入第三波冬季新冠疫情，情况又有所不同。许多人从最近的感染或疫苗接种中对新冠病毒产生了免疫力，但在近期感染呼吸道合胞病毒或流感的人比较少，这给流感和呼吸道合胞病毒的大规模卷土重来创造了条件，它们会提前汹涌来袭。
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Any potential interference during the present tripledemic winter will become more obvious once epidemiologists can look back on the season and see if each virus took its turn. Already, there are indicators that the fall surges of RSV and flu might have peaked, while Covid is on the upswing after the winter holidays. But there are still several cold months to come, providing ample opportunity for any of the trio to rise again.

如果流行病学家回顾这个季节，看看每一种病毒是否交替出现，那么当下冬天“三重流行病”疫情中出现的任何潜在干扰都会更加明显。有迹象表明，秋天激增的呼吸道合胞病毒和流感可能已达到高峰，而新冠病毒在寒假过后呈现上升趋势。但接下来还有几个寒冷的月份，“三重流行病”中的每一种病毒都有充足的机会卷土重来。

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