Astroviruses may not be well known, but they are very common and are the leading cause of diarrhea in children. As many as 90% of children are thought to have had an astrovirus infection by the time they are nine years old. Astrovirus is transmitted through through water that has fecal contamination containing the virus, and is often found in wastewater. Astroviruses are also tough; they are not inactivated by alcohols, bleach, or many detergents, and can withstand 50ºC temperatures for as much as an hour. There are no vaccines for astroviruses, and adults tend to have immunity from infections when they were young.
Reporting in Nature Communications, researchers have now revealed the mechanism that human astroviruses use to infect human cells.
"We uncovered a really important part of the virus lifecycle, and now we know exactly where on the virus this important interaction with the human receptor occurs," said corresponding study author Rebecca DuBois, a professor at the University of California, Santa Cruz. "Now we can develop vaccines that will target it and block that interaction; it really guides future vaccine development."
Scientists have previously shown that astroviruses can bind to a human protein known as the neonatal Fc receptor. This receptor normally aids the developing infant, and helps antibodies move to the bloodstream in adults.
In this study, the researchers developed models of astroviruses and the neonatal Fc receptor to determine how they bind. X-ray crystallography showed that astroviruses can bind to the same location as antibodies do on the neonatal Fc receptor.
"The virus is hijacking the pathway that humans use for beneficial purposes to get inside the cell," DuBois said. "I think that's one of the most exciting findings. We discovered exactly how the virus is using this receptor to sneak into our cells."
The investigators also found that there are some treatments that have already been approved by the FDA for other purposes, which could target the neonatal Fc receptor and potentially reduce the likelihood that astroviruses can bind to it. Now the researchers are interested in possibly repurposing some of these drugs as astrovirus treatments.
The team is also exploring the possibility of developing an astrovirus vaccine. The site where the virus binds to the receptor also seems to mutate frequently, which may indicate that a vaccine targeting multiple strains would be necessary for efficacy.
"If we can make a vaccine that is multivalent, we can protect against many strains of the virus," DuBois said.
Sources: University of California - Santa Cruz, Nature Communications
