Differential susceptibility of SARS-CoV-2 in animals: Evidence of ACE2 host receptor distribution in companion animals, livestock and wildlife by immunohistochemical characterisation.

Fabian Z X Lean1 Alejandro Núñez1 Simon Spiro2 Simon L Priestnall3 Sandra Vreman4 Dalan Bailey5 Joe James6 Ethan Wrigglesworth2 Alejandro Suarez-Bonnet3 Carina Conceicao5 Nazia Thakur5 Alexander M P Byrne6 Stuart Ackroyd1 Richard J Delahay7 Wim H M van der Poel4 Ian H Brown6 Anthony R Fooks6 Sharon M Brookes6
Affiliations 7 institutions
  1. Department of Pathology and Animal Sciences, Animal and Plant Health Agency (APHA), Addlestone, Surrey, UK.
  2. Wildlife Health Services, Zoological Society of London, London, UK.
  3. Department of Pathobiology and Population Sciences, The Royal Veterinary College, North Mymms, UK.
  4. Wageningen Bioveterinary Research, Lelystad, The Netherlands.
  5. The Pirbright Institute, Woking, Surrey, UK.
  6. Department of Virology, APHA, Addlestone, Surrey, UK.
  7. National Wildlife Management Centre, APHA, Sand Hutton, York, UK.

Abstract

Angiotensin converting enzyme 2 (ACE2) is a host cell membrane protein (receptor) that mediates the binding of coronavirus, most notably SARS coronaviruses in the respiratory and gastrointestinal tracts. Although SARS-CoV-2 infection is mainly confined to humans, there have been numerous incidents of spillback (reverse zoonoses) to domestic and captive animals. An absence of information on the spatial distribution of ACE2 in animal tissues limits our understanding of host species susceptibility. Here, we describe the distribution of ACE2 using immunohistochemistry (IHC) on histological sections derived from carnivores, ungulates, primates and chiroptera. Comparison of mink (Neovison vison) and ferret (Mustela putorius furo) respiratory tracts showed substantial differences, demonstrating that ACE2 is present in the lower respiratory tract of mink but not ferrets. The presence of ACE2 in the respiratory tract in some species was much more restricted as indicated by limited immunolabelling in the nasal turbinate, trachea and lungs of cats (Felis catus) and only the nasal turbinate in the golden Syrian hamster (Mesocricetus auratus). In the lungs of other species, ACE2 could be detected on the bronchiolar epithelium of the sheep (Ovis aries), cattle (Bos taurus), European badger (Meles meles), cheetah (Acinonyx jubatus), tiger and lion (Panthera spp.). In addition, ACE2 was present in the nasal mucosa epithelium of the serotine bat (Eptesicus serotinus) but not in pig (Sus scrofa domestica), cattle or sheep. In the intestine, ACE2 immunolabelling was seen on the microvillus of enterocytes (surface of intestine) across various taxa. These results provide anatomical evidence of ACE2 expression in a number of species which will enable further understanding of host susceptibility and tissue tropism of ACE2 receptor-mediated viral infection.

Supporting text Virus Host Location
ACE2 54 felids 2 immunohistochemistry 11 mustelids 6 SARS-CoV-2 550 Angiotensin-Converting Enzyme 2 177 COVID-19 425 Receptors, Virus 204 Animals 1948 Animals, Wild 187 Cat Diseases 67 Cats 120 Cattle 126 Cattle Diseases 47 Chiroptera 371 Ferrets 79 Livestock 20 Mink 48 Pets 25 SARS-CoV-2 453 Sheep 34 Sheep Diseases 14 Spike Glycoprotein, Coronavirus 274 Sus scrofa 30

Evidence records

1 total
Functional Mechanism
1 records · 1 evidence types
Evidence type
1 records
OVE4962
Key finding

ACE2 receptor expression was limited to nasal turbinate, trachea and lungs of cats and only nasal turbinate of golden Syrian hamsters, revealing restricted receptor distribution linked to SARS‑CoV‑2 entry.

Virus
Host
Location
Not specified
Supporting text

The presence of ACE2 in the respiratory tract in some species was much more restricted as indicated by limited immunolabelling in the nasal turbinate, trachea and lungs of cats (Felis catus) and only the nasal turbinate in the golden Syrian hamster (Mesocricetus auratus).

Method
immunohistochemistry
Receptors
ACE2