Protocadherin-1is an hantavirus receptor

A global team of investigators has identified a key protein involved in Hantavirus Pulmonary Syndrome (HPS), a serious and sometimes fatal respiratory disease, according to research published in the journal Nature.

Specifically, a cell-surface receptor protein called protocadherin-1 (PCDH1), commonly associated with human asthma, is responsible for facilitating lung cell infection and triggering HPS.

For decades, scientists have been attempting to identify the host molecules that mediate hantavirus infection and lead to HPS, which has a case fatality rate of 35-40 percent. Currently there are no licensed vaccines, prophylactics, or therapeutics to prevent or treat this highly pathogenic disease, which is transmitted to humans by infected rodents.

Through a genetic screen, the research team discovered that new world hantaviruses found in North and South America (Sin Nombre virus and Andes virus, respectively) were unable to infect cells when PCDH1 was "knocked out." Furthermore, when hamsters were depleted of PCDH1, then challenged with Andes virus, they were largely resistant to infection and lung injury.

"Our animal studies established that PCDH1 is essential for lung infection with new world hantaviruses, providing us with a viable target for blocking the disease," said co-first author.

"The discovery of the cellular receptor for hantaviruses allows for rational and logical drug and antibody design," said the researcher. "Stopping the virus from infecting lung tissue provides a route to eliminating HPS."

"While hantavirus infections are rare, they're expected to increase in the coming decades as temperatures across the globe rise due to climate change," commented another author. "And we need to be better prepared for that possibility."