To find out exactly what causes this antiviral ability, the scientists then incubated the vesicles with the viruses and imaged them under a microscope. They found that the viruses stuck to receptors on the surface of the vesicles, trapping them and rendering them unable to infect cells. In other words, the vesicles acted as a kind of bait. “Since the same receptors are found on the vesicles as on the cells, most viruses are bound to the vesicles and killed before they even reach the cells,” says Bleier.
In addition, the scientists also found that the stimulated vesicles contained larger amounts of microRNA – small strands of RNA – previously known to have antiviral activity.
Finally, the scientists wanted to see how a small change in temperature affects the quality and quantity of the vesicles excreted. To create a shell-based mimic of the human nose, they used small pieces of mucosal tissue taken from some patients’ noses and placed these small tissues, known as explants, in cell culture. They then lowered the temperature from 37 to 32 degrees Celsius, stimulated the tissue to upregulate TLR3, and collected the secreted vesicles.
They found that the cold reduced the tissue’s ability to secrete vesicles by 42 percent, and those vesicles had 77 percent fewer receptors that would bind them to a virus and neutralize it. “Even with that 5-degree drop for 15 minutes, it made a really dramatic difference,” says Amiji.
Noam Cohen, an otolaryngologist at the University of Pennsylvania, says this work sheds light on how viruses spread more easily in cold weather. (Cohen was not involved in this work, but previously mentored Bleier when he was a medical student.) “What this paper shows is that viruses, while incredibly simple, are incredibly smart,” he says. “They tweaked a cooler temperature to replicate it.”
Jennifer Bomberger, a microbiologist and immunologist at Dartmouth College, says one of the interesting points about the study was that the “vesicles weren’t just immune education,” meaning they weren’t just transmitting instructions for the immune system. Instead, she continues, “they actually exerted some of the actual antiviral effects themselves by binding to the virus.” However, she notes that looking at mucus from patients with real infections (rather than using a mimic virus) provides additional ones could provide insights into how these vesicles function.
The behavior of these vesicles is not the only reason why upper respiratory tract infections peak in winter. Previous work has shown that colder temperatures also reduce the work of antiviral molecules in the immune system called interferons. Viruses also tend to spread when people move indoors. Social distancing during the pandemic may also have meant people have less immunity to the viruses that cause the flu and RSV, both of which are part of the “triple disease” that emerged this winter.
Still, Amiji says that understanding exactly how the vesicles change could lead to some interesting ideas for therapies — because scientists might be able to control those changes. He visualizes it as “hacking” the vesicle “tweets”. “How can we increase the levels of these antiviral mRNAs or other molecules to have a beneficial effect?” he asks.
In light of the Covid-19 pandemic, the team realizes there’s already a handy way you can help your nose in cold weather: masking. Noses can stay snuggly and snuggly under a mask – as any eyeglass wearer whose lenses are fogged up from their warm breath can attest. “Wearing masks can have a double protective function,” says Bleier. “You certainly prevent the physical inhalation of the [viral] particles, but also by maintaining local temperatures, at least at a relatively higher level than in the outdoor environment.”
And here’s another idea to keep in mind: maybe it’s just time for a vacation somewhere warm.
https://www.wired.com/story/why-do-you-get-sick-in-the-winter-blame-your-nose/ Why Do You Get Sick in the Winter? Blame Your Nose