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 Lean,Richard J Delahay,Carina Conceicao,Anthony R Fooks,Alejandro Núñez,Simon L Priestnall,Alejandro Suarez‐Bonnet,Ethan Wrigglesworth,Simon Spiro,Wim H M Van Der Poel,Stuart Ackroyd,Sandra Vreman,Dalan Bailey,Ian H Brown,Alexander M.P Byrne,Joe James,Sharon M Brookes,Nazia Thakur

doi:10.1111/tbed.14232

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.

Highlights

Angiotensin I converting enzyme 2 (ACE2) is a component of the renin-angiotensin-aldosterone system which plays a critical role in the homeostasis of blood pressure through its regulation of hydrolysis of angiotensin II (Hamming et al, 2007)
Intense membranous and variable cytoplasmic immunolabelling was present on cells expressing ACE2 protein of ferret (Figure 1a), dog, cat, golden Syrian hamster, pig (Sus scrofa domestica), little brown bat (Myotis lucifugus) and least horseshoe bat (Rhinolophus pusillus) (Supporting information Table S1)
Non-specific immunolabelling was not observed when anti-ACE2 primary antibody was replaced with a concentration matched rabbit IgG for each species described above (Figure 1d)

Summary

Introduction

Angiotensin I converting enzyme 2 (ACE2) is a component of the renin-angiotensin-aldosterone system which plays a critical role in the homeostasis of blood pressure through its regulation of hydrolysis of angiotensin II (Hamming et al, 2007). The susceptibility of companion animals to severe acute respiratory syndrome (SARS) coronavirus infection was first recognised in domestic cats (Felis catus) living among infected humans during the 2003 SARS-CoV outbreak in Hong Kong (Martina et al, 2003). Animals developed self-limiting, low grade respiratory diseases (sub-clinical) which did not require further veterinary intervention. Outbreaks of SARS-CoV-2 infection in mink farms have resulted in the emergence of novel virus variants with potential consequences for public health (Hoffmann et al, 2021; Larsen et al, 2021; Oreshkova et al, 2020; Oude Munnink et al, 2021), which has been reported in experimentally infected ferrets (Everett et al, 2021; Richard et al, 2020)

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