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A Trio of Flu Studies Point the Way to Better Treatment and Prevention

A Trio of Flu Studies Point the Way to Better Treatment and Prevention

As we head into flu season, researchers at The University of Texas at Austin are announcing the results of three flu studies: One suggests a possible new target for drugs to combat the flu; another study forecasts how effective this year's flu vaccine might be; and a third looks at ways to improve the process of identifying flu strains in the wild and thus improve how strains are selected for inclusion in each year's vaccine.

Tetanus shot. Photo by Blake Patterson (https://www.flickr.com/photos/blakespot/)

Better Off Dead

If an influenza virus invades a host cell and survives long enough to avoid detection, it commandeers the cell's machinery to churn out a legion of viral copies. These copies then burst out, ready to invade more cells. Fortunately, healthy people have an immune response that can stem the tide. In some cases, the cell recognizes that it's under attack and commits suicide, preferring a quick death to sticking around only to help the virus.

Jason Upton, assistant professor of molecular biosciences, and his colleagues discovered a key step in the process whereby a host cell detects that it has been invaded by the influenza A virus. A protein called DAI recognizes and binds directly to the RNA genome of the virus, which sets off a chain reaction that leads to cell death. They found that mice lacking DAI are unable to control the virus from replicating; when these mice have the flu, they succumb to a lethal respiratory infection caused by the virus, which underscores the key role the protein plays in protecting the host.

According to Upton, drugs that enhance this natural defense might help the host nip an infection in the bud.

"This paper is really the start of a new avenue of flu research, and may someday lead to therapeutics," Upton says.

The study was published October 13 in the journal Cell Host & Microbe. The LaMontagne Center for Infectious Disease, of which Upton is a member, published a more detailed summary of the work here.

Rating This Year's Flu Vaccine

Every year, the World Health Organization (WHO) tries to predict which strains of the flu virus will be the most prevalent in the human population during the next flu season, so that it can select which strains to target in that year's vaccine. According to the Centers for Disease Control and Prevention (CDC), when most circulating flu viruses are like the vaccine viruses, the vaccine reduces the risk of flu illness by about 50 to 60 percent. For example, the CDC estimated last year's flu vaccine was 59 percent effective.

In a paper posted on the preprint website arXiv.org, associate professor of mathematics Andrew Blumberg and his colleagues at Columbia Medical School studied how the genetic diversity of flu strains circulating in New York City related to the effectiveness of flu vaccines over a 24-year period. They found that the more genetically diverse the circulating flu strains in the previous few years, the less effective the next year's vaccine turned out to be.

"What it presumably means is that increased genetic diversity makes it less likely that the guesses incorporated in the flu vaccine are correct," says Blumberg.

Based on their analysis, they forecast the effectiveness of the 2016-17 flu vaccine at just 36 percent. Blumberg says, however, that this result should be taken with a grain of salt, as the relationship between diversity and effectiveness, while striking, was not clearly tight enough to allow precise prediction.

Selecting Better Strains

To study the flu strains circulating in a population, scientists have to be able to grow them in the lab.

Many have observed that the flu strains that grow the best in standard cell cultures—cultures derived from dog kidney cells or monkey cells—are not the same flu strains that grow the best in humans. The viruses change in ways that are different than they would in humans, due to the unique environment of the cell culture. That effect was thought to be small, but according to a recent study in the journal Virus Evolution from integrative biology professor Claus Wilke and his team, the effect is so large and widespread that it might affect most computational modeling efforts of flu evolution. This new insight could lead to better computer models and enable WHO to pick better vaccine strains.

Wilke also notes that cell cultures are improving: Just last year, researchers developed a new cell culture made from "humanized" dog kidney cells, meaning human genes were swapped in for dog genes in the cells. In this latest study, Wilke and his team found that flu strains grown in this cell culture become less adapted and more closely resembled the strains that grow well in humans.

Forecasts based on the strains that grow in this improved cell culture should be more accurate than those of the past—and that should ultimately enable the production of better vaccines.

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Friday, 27 January 2023

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