New Coronavirus has Different Receptor than SARS Virus

The SARS epidemic of 2002-2003 was short-lived, but a novel type of human coronavirus, called HCoV-EMC, is blamed for five deaths and several other cases of severe disease originating in countries in the Middle East. According to a study to be published in mBio®, the online open-access journal of the American Society for Microbiology, on December 11 <http://mBio.asm.org>, HCoV-EMC uses a different receptor in the human body than the SARS virus.

First identified in a patient inSaudi Arabiain June, nine laboratory-confirmed cases of HCoV-EMC infection have now been identified, five of whom have died. Cases of HCoV-EMC infection are marked by severe pneumonia and often by kidney failure. “This virus is closely related to the SARS virus, and looking at the clinical picture, it causes the same pattern of disease,” says Christian Drosten of theUniversityofBonn Medical Centrein German, a lead author of the study, which was funded in part by the European Commission project ANTIGONE.

Given the similarities, Drosten and his colleagues wanted to know whether HCoV-EMC and SARS virus might use the same receptor, a sort of molecular “dock” on human cells that the virus latches onto to gain entry to the cell. The receptor for SARS virus, called ACE2, is found mostly on pneumocytes deep within the human lung. Does HCoV-EMC used the same receptor? “The answer is a clear no,” says Drosten. “This virus does not use ACE2.” This leaves open the question what receptor the virus does use.

To help identify how HCoV-EMC might have originated and moved between humans and animals, the second part of the study focused on the animal species the virus can infect. SARS virus is closely related to viruses from bats, but Drosten says the virus changed in the transition from bats to civet cats to humans and could no longer infect bats, so SARS was not present in the wild and did not pass repeatedly from bats to humans like a classical zoonotic disease. “So the [SARS] virus lost its old host and gained a new one,” says Drosten.

Like SARS virus, HCoV-EMC is most closely related to coronaviruses from bats, but unlike SARS virus, this study found that HCoV-EMC can still infect cells from many different species of bats. “This was a big surprise,” says Drosten. “It’s completely unusual for any coronavirus to be able to do that – to go back to its original reservoir.” The virus is also able to infect cells from pigs, indicating that it uses a receptor structure that all these animals have in common. If that receptor is present in mucosal surfaces, like the lining of the lung, it is possible the virus could pass from animals to humans and back again, making animals an ongoing source of the virus that would be difficult or impossible to eliminate.

Drosten says work on HCoV-EMC will continue in many hospitals and laboratories. His own lab will continue the search for the HCoV-EMC receptor and will work on developing diagnostic tools to help identify cases of infection with the virus.

Drosten says he’s also driven to find the animal source of the virus, a crucial piece of information in managing a potential outbreak. The virus can infect bats with host ranges that extend all across Europe and into theArabian Peninsula.