Researchers have discovered why some stomach bugs hit us so hard — and spread so fast.
New research published Wednesday in Cell Host & Microbe found that stomach infections, like norovirus and rotavirus, are more contagious and more potent when the virus particles cluster together.
These findings may help treat — and even prevent — these viruses more effectively.
The research began in 2015, when the researchers were studying polioviruses for a different project. It was led by Dr. Nihal Altan-Bonnet, who focuses on host-pathogen connections at the National Heart, Lung and Blood Institute. The researchers were looking, in particular, at vesicles — groups of viruses that clump together under protective membranes — compared with free-ranging viruses. Was there any difference, they wondered, in how the clustered and stand-alone viruses attacked our bodies?
Before this new research, scientists thought individual particles of a virus spread illnesses more effectively. It seemed like basic arithmetic. If you have 1,000 virus particles, you have 1,000 chances for cells to become infected. If you have only 20 clusters of viruses, they have only 20 chances to attack cells. Right?
Nope. In 2015, the researchers discovered that the viral clusters were much more effective at attacking human cells. But those results were from laboratory experiments. Could the same hold true in real life?
According to this study, yes. There's strength in numbers. The virus particles glom together and become their own sort of organism, and then they bombard our tissues with an overwhelming dose of the illness.
"By being together, they infect an intestinal cell with a very high number simultaneously," Altan-Bonnet explains. "Multiple viruses go inside that same cell."
She likens the virus clusters to a Trojan horse — they enter the cell as one unit, and then once inside the cell they can attack very effectively.
"They cooperate and compensate for each other's insufficiencies," Altan-Bonnet says.
The viruses are not only more contagious in clusters but often cause more severe infections than the freestanding viruses. The mice and piglets in the researchers' experiments got much sicker, and stayed sick longer, when exposed to the virus clusters instead of individual viruses.
And the research indicates that the protective membrane around these viral clusters may help them pass unnoticed by the immune systems — making them even more difficult to fight off.
"These viruses are sort of in stealth mode," Altan-Bonnet says.
Robert Legare Atmar, a doctor and professor of infectious disease at Baylor College of Medicine, says these results are significant. "They further our knowledge of how these important viral enteric pathogens can cause infection and be transmitted," he explains.
"It helps us understand mechanisms of norovirus and rotavirus transmission better," says Atmar, who was not affiliated with this study. "Such understanding may help us design strategies and interventions to interrupt transmission."
Further research, he says, will very likely dive deeper into how these clusters are transmitted and how they operate within the body. "Can antivirals be developed that prevent the formation of these 'packets'?" he asks.
Stomach bugs affect millions of people every year. From cruise ships to the Olympics, outbreaks of norovirus and rotavirus can cause serious and difficult-to-treat stomach illnesses.
We tend to pick up these stomach infections by something called the "fecal-oral route," which is as gross as it sounds. Basically, it happens when you accidentally ingest poop — by drinking tainted water or chewing on your fingernails after touching an infected doorknob, for example. Usually, the illnesses cause stomach pain and diarrhea, but some people — especially children and the elderly — are at risk of dying from the viruses.
A rotavirus vaccine exists, but studies show it works only if administered before 15 weeks of age — making it difficult to give in many parts of the world. Norovirus, on the other hand, has neither a vaccine nor a specific drug to treat it.
The researchers focused on these viruses in part because they are difficult to treat and because many people infected with them are unable to work.
"There's a lot of economic costs, because it's so severe," Altan-Bonnet says.
But there is good news in all of this.
The researchers say their work will help others develop treatments to target these clusters, rather than the individual particles, which could provide a breakthrough in dealing with the notoriously difficult illnesses.
"This research is going to lead to the development of different types of antiviral drugs — ones that target clusters differently," Altan-Bonnet says. "One way to do it is by targeting the membranes."
Medications that penetrate the protective shell around the virus clusters could help our bodies fight them off more quickly and easily.
And there are other, more surprising ways others might use this research. For instance, Altan-Bonnet says, viruses such as polio are being used to target brain tumors. The research is in the early stages, but testing on humans has begun. The idea is that the researchers might be able to use polio clusters, rather than individual viruses, to attack the tumors more effectively.
"It would seem crazy, right?" she asks. "But if you don't have any other choices, it's actually not a bad approach."
In that case, knowing how to make viruses even more potent could be a good thing, she says.
Next, the NIH researchers want to know whether other virus clusters are equally as powerful. Previously, they've shown in the lab that rhinoviruses, or the common cold, can also be more powerful when they band together. They will examine droplets from sneezes and coughs to see whether colds and even the flu can be transmitted in potent clusters.
"My prediction is yes," Altan-Bonnet says. "It just makes so much sense now to think that viruses want to be transported together in large numbers."
Melody Schreiber (@m_scribe on Twitter) is a freelance journalist in Washington, D.C.
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