Scientists find way to boost virus-fighter in cells before infection is present
Researchers have discovered a way to trigger a preventive response to a flu infection without any help from the usual players – the virus itself or interferon, a powerful infection fighter.
The finding, in both mouse and human cells, suggests that manipulating a natural process could someday be an alternative way to not just reduce the severity of the flu, but prevent infection altogether.
“The flu vaccine needs to change every year because the virus is constantly mutating. What we’re doing is targeting a more fundamental process that is not specific to any particular strain of the virus,” said Jacob Yount, assistant professor of microbial infection and immunity at The Ohio State University and senior author of the study.
After showing in cells that altering the role of one protein can stop the virus in its tracks, Yount’s lab has begun using experimental drugs to test this flu prevention strategy in mice. Any possibility for human use is still many years away, but the scientists’ long-term goal is to develop a vaccine-independent method to prevent flu infections.
“If we were to have an outbreak of some pandemic influenza virus similar to what we experienced in 2009, I could envision using this technique to help people who are particularly vulnerable to infection,” he said. “It would work best if used before an infection, because the strategy prevents cells from becoming infected in the first place.”
The method involves raising the level of a protein that is known to be effective against all strains of influenza ever tested. The trick for infection prevention, however, is boosting that protein’s level in cells before the virus shows up. Doing that, the scientists discovered in this study, involves suppressing the function of another protein.
The protein effective against influenza is called IFITM3, (pronounced I-fit-M-3, for interferon-induced transmembrane protein 3).
Under natural conditions, IFITM3 is produced in large quantities only after the flu virus is present, so it can reduce the severity of infection. But the way it targets the virus – by trapping it and disabling its ability to make copies of itself – means that increasing the protein level before the flu ever arrives would prevent infection from occurring.
Enough IFITM3 is produced in all cells to maintain a small but steady presence, but it has a short lifespan. If a cell doesn’t see a need for its virus-fighting function, the protein is degraded. However, when flu virus does invade a cell, the cell cranks up production of interferon, which prompts increased production of IFITM3.
Interferon has another role, as well: telling an enzyme that degrades IFITM3 to hold off on that job so the IFITM3 level can stay high and fend off an influenza attack. This enzyme, also a protein, proved to be the silver bullet in Yount’s work on flu prevention.
The enzyme is called NEDD4 (pronounced Ned-4), and it degrades IFITM3 by attaching a small chain of molecules to it – a common process of protein clearing called ubiquitination.
In a series of experiments in mouse and human lung cells, Yount and colleagues showed that inhibiting NEDD4 from doing this job led to an accumulation of IFITM3 in the cells and greater resistance to infection by flu viruses.
IFITM3 is known to be important to humans because previous research has shown that it is the only identified protein containing a frequent genetic mutation linked to severe flu infections. Mice – and their cells – are effective models for this research because mice lacking the same IFITM3 protein are highly susceptible to flu infections.
Being able to stimulate this response is important for many reasons, not the least of which is keeping interferon out of the process. Interferon’s infection-fighting power is accompanied by severe side effects – most commonly associated with its former use as a treatment for Hepatitis C – that include, not surprisingly, flu-like symptoms.
“We figured out a way to induce just this single interferon response – the most important thing interferon does for flu,” Yount said. “That was a huge finding – that you don’t need an infection or interferon to increase the level of IFITM3. The steady-state level of the protein is enough to inhibit the virus if you get rid of NEDD4.”
Exactly how – and when – to get rid of NEDD4 remains an open question. Without this enzyme, embryonic mice cannot survive to birth, indicating it is important to fetal development. But later in life, lacking NEDD4 might not pose any health problems – which is why Yount is currently testing the effects of suppressing NEDD4 on adult mice.
The Latest on: Flu Prevention
via Google News
The Latest on: Flu Prevention
- How did COVID-19 precautions impact flu numbers in Denton County?on April 30, 2021 at 4:28 pm
For over a year health officials have been encouraging safety precautions to help stop the spread of COVID-19.
- Drop in flu cases in the Heartland during the pandemicon April 30, 2021 at 4:21 pm
If we hadn’t of done these measures with flu, we would have had flu and COVID, and so it really shows how obviously infectious COVID-19 is, but it also shows that we were doing those measures. It’s ...
- Dual vaccine could prevent COVID-19 and fluon April 30, 2021 at 3:22 pm
Pharmaceutical giant Moderna is developing a dual vaccine that could protect recipients from influenza and COVID-19. "If they combine the COVID-19 vaccine and the flu vaccine would you consider ...
- Fainting after Johnson & Johnson COVID-19 vaccination 164 times more common than post-flu shot: CDCon April 30, 2021 at 9:35 am
Prior to reports of rare but serious blood clotting with Johnson & Johnson’s COVID-19 vaccine, federal health authorities were investigating dozens of anxiety-related events and fainting episodes in ...
- Misleading flu statistics fuel ‘fake pandemic’ claims onlineon April 28, 2021 at 1:35 am
A graphic purporting to show that flu cases have fallen dramatically since 2020 has been shared by Facebook users worldwide alongside a claim it proves health authorities are falsely passing influenza ...
- Flu nearly non-existent this season, Capital Region doctors sayon April 24, 2021 at 8:40 am
Last year, 22,269 people were hospitalized for the flu in New York, according to the state Department of Health flu tracker. This year, the number of hospitalizations for the flu is at 692, according ...
- Going keto can cause flu-like symptoms - here are 5 tips to avoid or treat the keto fluon April 23, 2021 at 12:04 pm
The keto flu occurs as your body adapts to the keto diet and can result in symptoms like fatigue, nausea, and difficulty concentrating.
- State won't end flu reports early this year, despite lackluster seasonon April 23, 2021 at 9:09 am
Despite a decidedly lackluster flu season, the state Department of Public Health will continue to publish its flu reports through the end of the season. At this time last year, the state announced it ...
- The Flu's Return Puts Health Officials In 'Uncharted Territory'on April 22, 2021 at 3:08 pm
Public health measures in response to the coronavirus all but stopped the flu but, it's poised for a comeback.
- The Flu Vanished During Covid. What Will Its Return Look Like?on April 21, 2021 at 10:00 pm
The latest flu season, which normally would have run until next month, essentially never happened. After fears that a “twindemic” could batter the country, the absence of the flu was a much needed ...
via Bing News