title: Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replicative capability in mammalian cell lines.
abstract: A new human coronavirus (hCoV-EMC) has emerged very recently in the Middle East. The clinical presentation resembled that of the severe acute respiratory syndrome (SARS) as encountered during the epidemic in 2002/2003. In both cases, acute renal failure was observed in humans. HCoV-EMC is a member of the same virus genus as SARS-CoV but constitutes a sister species. Here we investigated whether it might utilize angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor. Knowledge of the receptor is highly critical because the restriction of the SARS receptor to deep compartments of the human respiratory tract limited the spread of SARS. In baby hamster kidney (BHK) cells, lentiviral transduction of human ACE2 (hACE2) conferred permissiveness and replication for SARS-CoV but not for hCoV-EMC. Monkey and human kidney cells (LLC-MK2, Vero, and 769-P) and swine kidney cells were permissive for both viruses, but only SARS-CoV infection could be blocked by anti-hACE2 antibody and could be neutralized by preincubation of virus with soluble ACE2. Our data show that ACE2 is neither necessary nor sufficient for hCoV-EMC replication. Moreover, hCoV-EMC, but not SARS-CoV, replicated in cell lines from Rousettus, Rhinolophus, Pipistrellus, Myotis, and Carollia bats, representing four major chiropteran families from both suborders. As human CoV normally cannot replicate in bat cells from different families, this suggests that hCoV-EMC might use a receptor molecule that is conserved in bats, pigs, and humans, implicating a low barrier against cross-host transmission. IMPORTANCE A new human coronavirus (hCoV) emerged recently in the Middle East. The disease resembled SARS (severe acute respiratory syndrome), causing a fatal epidemic in 2002/2003. Coronaviruses have a reservoir in bats and because this novel virus is related to SARS-CoV, we investigated whether it might replicate in bat cells and use the same receptor (angiotensin-converting enzyme 2 [ACE2]). This knowledge is highly critical, because the SARS-CoV receptor influenced pathology, and its localization in the deep respiratory tract is thought to have restricted the transmissibility of SARS. Our data show that hCoV-EMC does not need the SARS-CoV receptor to infect human cells. Moreover, the virus is capable of infecting human, pig, and bat cells. This is remarkable, as human CoVs normally cannot replicate in bat cells as a consequence of host adaptation. Our results implicate that the new virus might use a receptor that is conserved between bats, pigs and humans suggesting a low barrier against cross-host transmission.
authors.affiliation: Institute of Virology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Müller
authors.forename: V Stalin
authors.initials: VS
authors.lastname: Raj
authors.forename: Doreen
authors.initials: D
authors.lastname: Muth
authors.forename: Benjamin
authors.initials: B
authors.lastname: Meyer
authors.forename: Stephan
authors.initials: S
authors.lastname: Kallies
authors.forename: Saskia L
authors.initials: SL
authors.lastname: Smits
authors.forename: Robert
authors.initials: R
authors.lastname: Wollny
authors.forename: Theo M
authors.initials: TM
authors.lastname: Bestebroer
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.forename: Tasnim
authors.initials: T
authors.lastname: Suliman
authors.forename: Katrin
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Tabea
authors.initials: T
authors.lastname: Binger
authors.forename: Isabella
authors.initials: I
authors.lastname: Eckerle
authors.forename: Marco
authors.initials: M
authors.lastname: Tschapka
authors.forename: Ali M
authors.initials: AM
authors.lastname: Zaki
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
authors.forename: Bart L
authors.initials: BL
authors.lastname: Haagmans
authors.forename: Christian
authors.initials: C
authors.lastname: Drosten
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002460:Cell Line; D017934:Coronavirus / Q000502:physiology*; D018352:Coronavirus Infections / Q000453:epidemiology / Q000821:virology; D058507:Host Specificity; D006801:Humans; D008322:Mammals; D008877:Middle East / Q000453:epidemiology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D053585:Virus Attachment; D014779:Virus Replication
chemical_list: D011991:Receptors, Virus; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2