A case of viral interference?

The development of ‘tripledemia’ this winter is one of several strange trends among respiratory virus infections in recent years. It turns out that viruses can block each other and take turns to dominate.

Three years into the pandemic, covid-19 is still going strong, causing wave after wave as the number of cases spikes, falls and then climbs again. But this past fall saw something new, or rather, something old: the return of the flu. In addition, the respiratory syncytial virus (RSV), a virus that makes few headlines in normal years, flared on its own rise, creating a “triple epidemic.”

The surges in these old foes were particularly surprising because influenza and RSV all but disappeared during the first two winters of the pandemic. Even more surprising, a particular version of the flu may have died out during the first Covid pandemic. The World Health Organization’s surveillance program hasn’t definitively detected the B/Yamagata flu strain since March 2020. “I don’t think anyone would take a chance and say it’s gone,” says Richard Webby, a virologist at St. Jude Children’s Research Hospital in Memphis. But, he adds, “we hope it’s squeezed out.” Such an extinction would be a super rare event, Webby says.

But then, the last few years have been very unusual times for human-virus relationships, and lockdowns and masks went a long way toward preventing the flu and RSV from infiltrating human nostrils. Still, Webby thinks another factor may have kept them in check as Covid raged. It’s called viral interference, and it simply means that the presence of one virus can block another.

Viral interference can occur in individual cells in the laboratory, and in individual animals and people who are exposed to multiple viruses, but it can also affect entire populations, if enough people contract one virus to hinder the flourishing of others on a large scale. . This results in waves of individual virus infections taking turns to dominate. “Looking back at the last two years, I’m pretty sure Covid can certainly block the flu and RSV,” Webby says.

It would not be the first time that scientists have observed such patterns. In 2009, for example, the virus to fear was swine flu, which jumped from pigs to people in the spring of that year. It seemed about to rise when autumn came, 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 center stage for a number of weeks before swine flu regained dominance. That flu strain then delayed the typical fall RSV surge by up to two and a half months.

Interference running

There are several ways that interference can occur in the body. One occurs when two viruses use the same molecule to enter host cells. If Virus A gets there first and grabs onto all those molecular doorknobs, then Virus B is out of luck.

Another type of interference could occur if two viruses compete for the same resources within the cell, such as the machinery to make new viral proteins or the means to escape from that cell and infect others. “Think of it like a race between two viruses,” says Webby.

But the best-understood method of interference concerns a defensive molecule called interferon that is produced by the cells of all animals with backbones (and possibly some invertebrates as well). In fact, viral interference is the reason interferon got its name to begin with. When a cell detects a virus, any virus, it begins to produce interferon. And that, in turn, turns on a whole host of defensive genes. Some of the products of these genes function within the cell or at its boundaries, where they prevent additional viruses from entering and block the replication or exit of viruses already present from the cell.

Cells secrete interferon into their environment, warning other cells to raise their guard. The result of all this: if a second virus appears, the cells already have their defenses activated and it is possible that they can block it.

This “beware” message can spread throughout the body. So in theory, contracting a respiratory virus like rhinovirus could activate defenses in, say, the gut, protecting the same person from a completely different virus, like norovirus. But the situation will vary depending on the viruses involved, the amount of interferon produced, and other factors. “Most viruses have ways of neutralizing the interferon system,” says Ganes Sen, a virologist at the Cleveland Clinic in Ohio who wrote about interferon-virus interactions for the Annual Review of Virology in 2015. “It’s a pull. of war.”

Scientists study that back and forth in animals and other systems in the lab. For example, Ellen Foxman, an immunologist at Yale School of Medicine, investigates viral interactions in tissues grown in the lab from real human airway cells. In one experiment, she studied swine flu and a typical representative of the rhinovirus family. When the researchers infected human tissue first with the rhinovirus and then with swine flu, the interferon prevented the flu from taking hold. In similar studies, she found that rhinovirus infection also interfered with subsequent SARS-CoV-2 infection.

It’s dubious to extrapolate from tissues in the lab to people or populations, but Foxman believes the studies reflect biological truth. “It’s likely that if you get infected with a rhinovirus, that will make you relatively resistant to another virus for some time,” he says. Foxman speculates that the protective effect is likely to last for days or weeks.

But don’t count on a cold giving you temporary immunity against other viruses. Interference is not guaranteed: it is 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 secondary bacterial infection.

In the ongoing pandemic, it is still difficult to say what role, if any, interference played in shutting down RSV and flu in populations around the world. During the first wave of covid in 2020, Foxman believes there were not enough people with covid to interfere with other viruses on a large scale. (RSV experienced an unusual summer spike in 2021 as people eased up on mask-wearing and other precautions.)

But by the second winter of Covid, in 2021-22, Webby thinks he sees evidence of interference at the population level. Influenza was starting to rise in the fall, he says, but then the omicron variant of Covid burst onto the scene. Flu rates fell, even as people returned to work and school and traveled on vacation. The coronavirus had a big advantage that season, he says, because so many people still lacked immunity. It does not mean that Covid will always outperform influenza in the future.

In the third winter of Covid now underway in the northern hemisphere, conditions are different once again. Many people now have immunity to Covid, from a recent attack or from vaccination, but fewer have experienced RSV or flu in recent memory. That set the stage for Flu and RSV to stage a massive double comeback, hitting early and hard.

Any possible interference during the tripledemic winter of 2022-23 will become more apparent once epidemiologists can look back on the season and see if each virus had its turn. There are already indicators that the fall waves of RSV and flu may have peaked, while Covid is on the rise after the winter break. But there are still several cold months to come, providing ample opportunity for any of the trio to rise again.

This article originally appeared in Knowable Magazine, an independent journalism effort of Annual Reviews. Sign up for the newsletter.

Source: news.google.com