| Abstract |
In recent years many emerging viruses threatening human health were
discovered and found to have their major host reservoir in bats. Rabies,
Ebola, Henipah and Coronaviruses are the most prominent under these
zoonotic pathogens, where especially the emergence of severe acute
respiratory syndrome (SARS) coronavirus in 2002 and the recent appearance
of Middle East respiratory syndrome (MERS) coronavirus had gained global
awareness. Great effort has been invested to uncover the course of events
of their introduction to the human population. Coronaviruses may be
exemplary for many zoonotic RNA viruses, so that the study of their
genesis expected to provide insights into basic questions about viral
zoonosis. For coronaviruses the recognition of a specific receptor by the
viral glycoprotein appears to be a major constrain of interspecies
transmission. Therefore, it is important to address the question whether a
large shift in receptor specificity was necessary for their transmission
to humans. The closest related relative to SARS coronavirus was identified
in bats of the genus Rhinolophus in South-East of China, but until today
no coronavirus was isolated from bats. What is known is that these viruses
are not able to utilise the same receptor as the human SARS coronavirus,
the human angiotensin converting enzyme 2 (ACE2). The aim of our studies
was to identify the receptor of these bat SARS-like coronaviruses, which
would help to estimate the likelihood of their transmission to humans. We
therefore used three different glycoproteins of bat SARS-like
coronaviruses isolated from Rhinolophus bats in China, Bulgaria and Spain
and tried to identify their cellular receptors analysing cell lines of 14
different bat species, in binding as well as infection assays.
Unfortunately neither binding nor infection could be observed for the
spike proteins tested. We also tested known coronavirus receptors like
human ACE2, aminopeptidase N (APN) and dipeptidylpeptidase 4 (DPP4) and
successfully cloned Rhinolophus ACE2 and DPP4. None of these proteins
facilitated binding or infection in transient expression. This indicates
that bat SARS-like coronaviruses utilise a novel coronavirus receptor. In
contrast, we could show that SARS coronavirus can utilise ACE2 of two
Rhinolophus species living in Europe, indicating that a proposed switch in
receptor specificity may not be obligatory for the precursor of SARS-CoV
to cross the species barrier. It may further suggests that bats are
reservoir to at least two different lineages of coronaviruses, which
differ in their receptor usage.
|
|---|
