Authors: Heather Jones, Future Science Group
A new study published in mBio, a journal by the American Society for Microbiology, has used mice to demonstrate that obesity could contribute to the variation and consequent viral drift observed in the influenza virus, which results in the need for the creation of yearly influenza vaccines.
Obesity is an ever-increasing threat to public health, with currently 50% of the adult population worldwide considered overweight or obese.
Previous research has demonstrated that individuals who are obese have higher influenza viral loads and that they shed the virus for longer. Further, animal obesity studies have revealed that the virus can spread deeper into the lungs and for longer periods of time.
Each new year brings a new vaccine as the virus continues to mutate and drift. In this study, a group of researchers hypothesized that the obese microenvironment may allow the influenza virus to change more rapidly and therefore accelerate viral drift.
In the study, the team monitored lean and obese mice infected with influenza for 3 days, allowing time for the virus to replicate. They then obtained the viruses from the two mice and used them to infect obese and lean mice respectively. “We wanted to mimic what would happen during an epidemic where the virus goes from one person to the next,” explained Stacey Schultz-Cherry (St. Jude Children’s Research Hospital, TN, USA). “What happens if a virus goes from a lean person to a lean person to a lean person versus an obese person to an obese person to an obese person.”
They discovered differences between the viruses among the two groups of mice. In the obese mice, minor variants rapidly emerged, giving rise to increased viral replications and consequently enhanced virulence in wild-type mice.
“When you get infected with flu, it’s not just one virus, it’s a population. It’s like a little cocktail party and in this case, the cocktail party in the obese mice was a whole different matter,” commented Schultz-Cherry. “There were different populations and some of those viruses were more virulent than the strains that went from lean mouse to lean mouse.”
It’s a cocktail party none of us want to be invited to. The researchers observed a blunted interferon response in the obese mice, resulting in increased viral replication. The increased diversity of the influenza viral population in the obese mice therefore correlated with the decreased type I interferon responses. Further, when treating obese mice with recombinant interferon, the team observed a reduction in viral diversity, suggesting that the delayed antiviral responses exhibited in obesity may permit the emergence of a more virulent influenza population.
“We want to be careful about extrapolating too much from a mouse experiment, but the study does suggest that because of the problem with how cells respond to flu in an obese environment, individuals who are obese don’t have good antiviral responses. They are delayed. They are blunted,” commented Schultz-Cherry. “Obesity allows the virus to get in, replicate faster and make more mistakes. Some of those mistakes are potentially beneficial for the virus.”
The team is planning to conduct further research into the cellular mechanisms behind the viral shifting, along with investigating whether their findings can be translated to human populations.