How one virus can block another 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. More than 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". 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. "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. 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 Covid19 raged. It's called viral interference, and it simply means that the presence of one virus can block another. 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. 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. Running interference 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. 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. 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. 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. 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 <…>. 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 <…>. 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. Sources: https://knowablemagazine.org/article/health-disease/covid-rsv-flu-viral-interference https://www.bbc.com/future/article/can-you-get-two-viruses-at-the-same-time
