Membrane ectopeptidases targeted by human coronaviruses.
Six coronaviruses, including the recently identified Middle East respiratory syndrome coronavirus, are known to target the human respiratory tract causing mild to severe disease. Their interaction with receptors expressed on cells located in the respiratory tract is an essential first step in the infection. Thus far three membrane ectopeptidases, dipeptidyl peptidase 4 (DPP4), angiotensin-converting enzyme 2 (ACE2) and aminopeptidase N (APN), have been identified as entry receptors for four human-infecting coronaviruses. Although the catalytic activity of the ACE2, APN, and DPP4 peptidases is not required for virus entry, co-expression of other host proteases allows efficient viral entry. In addition, evolutionary conservation of these receptors may permit interspecies transmissions. Because of the physiological function of these peptidase systems, pathogenic host responses may be potentially amplified and cause acute respiratory distress.
Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, the Netherlands.
Berend Jan
BJ
Bosch
Department of Viroscience, Erasmus Medical Center, 3000 CA Rotterdam, the Netherlands.
Saskia L
SL
Smits
Department of Viroscience, Erasmus Medical Center, 3000 CA Rotterdam, the Netherlands. Electronic address: b.haagmans@erasmusmc.nl.
Bart L
BL
Haagmans
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D017934:Coronavirus / Q000502:physiology*; D018352:Coronavirus Infections / Q000378:metabolism* / Q000821:virology*; D019143:Evolution, Molecular; D054884:Host-Pathogen Interactions; D006801:Humans; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism*; D056189:Viral Tropism
D011991:Receptors, Virus; D010447:Peptide Hydrolases