Literature detail

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.
PMID 34245662 2022 Transbound Emerg Dis eng ppublish
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Article

Publication summary

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.

ACE2 felids immunohistochemistry mustelids SARS-CoV-2 Angiotensin-Converting Enzyme 2 COVID-19 Receptors, Virus Animals Animals, Wild Cat Diseases Cats Cattle Cattle Diseases Chiroptera Ferrets Livestock Mink

Structured evidence records

Evidence records

5 total
4 records
Extraction confidence 0.88
Key finding

ACE2 receptor was detected in the lower respiratory tract of mink but absent in ferrets, indicating species differences in potential susceptibility to SARS-CoV-2.

Virus
Location
Not specified
Supporting text

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.

Method
immunohistochemical characterisation
Sample type
lower respiratory tract
Experimental system
in vitro tissue immunohistochemistry
Extraction confidence 0.88
Key finding

ACE2 receptor was detected in the respiratory tract of cats and in the nasal turbinate of golden Syrian hamsters, suggesting possible tissue-specific susceptibility to SARS-CoV-2.

Virus
Location
Not specified
Supporting text

ACE2 was present in the respiratory tract in cats (Felis catus) and only the nasal turbinate in the golden Syrian hamster (Mesocricetus auratus).

Method
immunohistochemical characterisation
Sample type
respiratory tract
Experimental system
in vitro tissue immunohistochemistry
Extraction confidence 0.88
Key finding

ACE2 receptor was detected on bronchiolar epithelium of several species including sheep, cattle, badger, cheetah, tiger, and lion, supporting the presence of SARS-CoV-2 entry receptor in diverse mammals.

Virus
Host
Location
Not specified
Supporting text

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.).

Method
immunohistochemical characterisation
Sample type
bronchiolar epithelium; lung
Experimental system
in vitro tissue immunohistochemistry
Extraction confidence 0.88
Key finding

The serotine bat expressed ACE2 in nasal mucosa whereas pigs, cattle, and sheep lacked detectable ACE2, indicating possible species restriction of SARS-CoV-2 receptor expression.

Virus
Location
Not specified
Supporting text

ACE2 was present in the nasal mucosa epithelium of the serotine bat (Eptesicus serotinus) but not in pig (Sus scrofa domestica), cattle or sheep.

Method
immunohistochemical characterisation
Sample type
nasal mucosa epithelium
Experimental system
in vitro tissue immunohistochemistry
1 records
Extraction confidence 0.96
Key finding

SARS-CoV-2 receptor ACE2 was detected in specific tissues of multiple animal species, including the lower respiratory tract of mink but absent from ferrets, indicating species-specific receptor distribution relevant to viral entry.

Virus
Location
Not specified
Supporting text

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. Here, we describe the distribution of ACE2 using immunohistochemistry (IHC) on histological sections derived from carnivores, ungulates, primates and chiroptera. Comparison of mink and ferret respiratory tracts showed substantial differences, demonstrating that ACE2 is present in the lower respiratory tract of mink but not ferrets.

Method
immunohistochemistry
Receptors
ACE2