Scientists had long believed that viruses act independently to infect cells, until 2015, when researchers at the National Institutes of Health illustrated that enteroviruses such as poliovirus can travel collectively in packets. Now they have strong evidence that a similar mechanism can promote the spread of stomach viruses. The discovery could spark ideas for new therapies to prevent and treat common illnesses like rotavirus and norovirus.
A team led by Nihal Altan-Bonnet, Ph.D., head of the Laboratory of Host-Pathogen Dynamics at NIH's National Heart, Lung, and Blood Institute, previously made a novel discovery of what they call a “Trojan horse” mode of viral transmission. In their earlier study, which appeared in Cell, Altan-Bonnet and her collaborators found that after replicating in cells, poliovirus particles assemble in groups and are packaged in double-layered lipid-enriched vesicles. The vesicles travel to the next host cell, evading immune detection, then deposit the virus into the cell.
This time around, the researchers focused on norovirus and rotavirus, two RNA viruses that mainly spread through the accidental consumption of food or water contaminated with an infected person’s stool. Both diseases can cause stomach illnesses including diarrhea and in some severe cases lead to death. Norovirus in particular is highly contagious and has led to outbreaks in crowded spaces, most notably on cruise ships, daycare centers, classrooms and nursing homes.
The researchers studied fecal samples from humans and animals and indeed found that the viruses live as clusters inside membrane-cloaked packets. In addition, the vesicles were significantly more infectious than free-floating viruses within the samples. The clusters allowed the virus to spread more aggressively and increased the severity of the disease, the team reported in the journal Cell Host & Microbe.
“Our findings indicate that vesicle-cloaked viruses are highly virulent units of fecal-oral transmission and highlight a need for antivirals targeting vesicles and virus clustering,” said Altan-Bonnet in a release.
Although there are rotavirus vaccines on the market, there is currently no way to protect against norovirus. Vaxart is developing a vaccine based on its adenovirus type 5 vector-based platform that's designed to spark immune actions in the gastrointestinal tract. The vaccine recently completed a phase 1b study, during which more than 90% of recipients in the high-dose group had at least a twofold increase in norovirus-blocking antibodies 28 days after dosing.
Still, there is a high demand for new ways to fight diseases that strike the gut, which is where the NIH team's new insights could prove valuable. The researchers haven't quite figured out why virus vesicles render greater infectious powers, but they have a few thoughts. First, the vesicles could protect the viruses from our immune defense system, possibly by making them invisible to the antibodies in the stool or gut of the host. Once the vesicles arrive at their destination, they can unload several viruses all at once.
Thus the viruses are “going in with, essentially, an army,” Altan-Bonnet recently said at an NIH event. “A single viral genome, entering a cell, is going to be up against a lot until it gets enough viral proteins made and viral genome replicated to take over the entire cell.”