CIDRAP
Lisa Schnirring
Staff Writer
Dec 11, 2012 (CIDRAP News) – Experiments on the novel coronavirus
that has infected patients from three Middle Eastern countries show that
the receptor it uses to infect human cells is different from the one
used by its relative the SARS virus and that it can infect cells from a
range of animals, according to a study released today.
Both findings have implications for public health, as experts rush
to assess the threat and develop tools to battle the emerging virus,
which has so far led infected at least 9 people, causing 5 deaths, in
Saudi Arabia, Qatar, and Jordan. The study was conducted by researchers
from Germany and the Netherlands and appears today in mBio, the online journal of the American Society for Microbiology (ASM).
The virus, called hCoV-EMC, has been linked to two illness
clusters, including one that involved healthcare workers at a Jordanian
hospital. All of the patients with confirmed infections had pneumonia,
and several had severe renal complications.
The European Centre for Disease Prevention and Control (ECDC) said
recently that though the case clusters raise the possibility of
human-to-human transmission, so far there is too little information to
confirm or rule it out. Regardless, concerns about transmission risk
have prompted intensive monitoring of close contacts of case-patients
and reminders about steps to protect healthcare workers.
Christian Drosten, MD, lead author of the study and director of
the Institute of Virology at the University of Bonn Medical Centre in
Germany, said in an ASM press release today, "This virus is closely
related to the SARS virus, and looking at the clinical picture, it
causes the same pattern of disease."
One question the research team wanted to explore was whether the
hCoV-EMC and SARS viruses use the same receptor to enter human cells.
The SARS virus uses the angiotensin-converting enzyme 2 (ACE2) receptor,
which is mainly found on pneumocytes deep in human lungs. Drosten said
individuals needed to inhale great numbers of SARS viruses for enough to
reach deep into the lungs and take root, a factor that limited its
spread mainly to healthcare workers and people who lived in overcrowded
housing in Hong Kong.
The researchers found that hCoV-EMC clearly does not use ACE2,
Drosten said in the press release But the virus could use another,
still-unknown receptor in human lungs that is easier to access and could
make the virus more infectious than SARS, he added.
In the second part of the study, the group conducted a set of
experiments to shed light on how the virus might have originated and
moved between humans and animals. Genetic sequencing of an hCoV-EMC
sample from a Saudi man who died in June showed that the virus most
closely resembles coronaviruses found in bats. Some of the patients with
confirmed infections had visited farms before they got sick.
Drosten said the SARS virus changed after it jumped from bats to
civets to humans, rendering it unable to infect bats again. However, he
said researchers were surprised to see that hCoV-EMC can infect cells
from many different species. The group found that it could enter cells
from four major bat families, pigs, and primates. "It's completely
unusual for any coronavirus to be able to do that—to go back to its
original reservoir," he said.
The team reported that the findings suggests all the animals could
share a common receptor, and if the receptor is present on mucosal
surfaces such as the lining of the lung, the virus could pass back and
forth between animals and humans, making it difficult or even impossible
to eliminate.
Drosten said his lab is still trying to identify the hCoV-EMC
receptor and that more work on the virus is under way at many other
hospitals and labs.
Kathryn Holmes, PhD, professor emerita in the University of
Colorado School of Medicine's Department of Microbiology, told CIDRAP
News that the group's findings are exciting news. She is a coronavirus
expert whose work has focused on characterizing receptors for several
coronaviruses.
She said there are several different receptor proteins for
coronaviruses and it will be interesting to see what the receptor or
receptors are for the new coronavirus. It's not possible, she added, to
predict the receptor solely from the genetic sequence of the virus'
spike protein, the glycoprotein that mediates its entry into host cells.
The discovery that the virus grows well in multiple species
without adaptation is important, but it does not necessarily predict
whether each of the species is sickened by the virus, she said.
Scientists have a lot of questions to answer about the new virus,
such as its tissue tropism, virulence mechanism, and transmission
routes, Holmes said, adding, "It is amazing how quickly data from this
newly discovered virus is flowing from many labs."
Rapid identification of reservoir hosts, routes of transmissions,
and virulence determinants in different hosts will help reduce human
contact with potential animal reservoirs, and sensitive assays to detect
viral RNA and proteins are being developed and used to analyze the
epidemiology of the virus in humans and animals, Holmes said.
She said the virus has apparently been discovered before any
widespread in humans, and current research will establish assays to
allow health officials to rapidly evaluate any potential spread of the
new virus to new hosts or different regions or from human to human.
Muller MA, Raj VS, Muth D, et al. Human coronavirus EMC
does not require the SARS-coronavirus receptor and maintains broad
replicative capability in mammalian cell lines. mBio 2012 Dec 11 [
Abstract]
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