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

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 ACE2This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

SARS-CoV-2 variants of concern alpha, beta, gamma and delta have extended ACE2 receptor host ranges

“…Recently, we demonstrated tissue-specific differences in ACE2 expression between various animals, e.g. ACE2 was present in the nasal mucosa epithelium of Eptesicus serotinus (serotine bat) but not in pigs ( Sus scrofa domestica ) [37], which may provide some mechanistic insight into the varying susceptibility of hosts to SARS-CoV-2. Beyond entry, various species-specific restrictions, for example at the level of the innate immunity response, may also be playing a role.…”

Experimental and natural infections of severe acute respiratory syndrome-related coronavirus 2 in pets and wild and farm animals

“…Furthermore, the evaluation of the binding contact between ACE2 of those animals with RBD in the S-protein of SARS-CoV-2 predicted medium susceptibility to SARS-CoV-2 infection, at the same level as documented in the cat [108]. In addition, ACE2 receptors were expressed in the bronchiole epithelia of cattle and sheep but not in the nasal mucosa and alveoli [109]. By contrast, ACE2 receptors in cats were expressed in alveoli and Type I pneumocytes [109].…”

“…In addition, ACE2 receptors were expressed in the bronchiole epithelia of cattle and sheep but not in the nasal mucosa and alveoli [109]. By contrast, ACE2 receptors in cats were expressed in alveoli and Type I pneumocytes [109]. However, an in vivo study found that the infectious virus was not detected in cattle.…”

“…The appearance of the clinical signs may be explained by the ACE2 expressions in the ciliated bronchial epithelium cells from tigers and lions and in the endothelial blood vessels within the alveolar septa in tigers [109]. In view of the expressions of ACE2 in the respiratory tracts of big cats [109], the increasing number of natural infections of SARS-CoV-2 in these animals and the transmission of the virus from asymptomatic carriers [29,30,[59][60][61]65,66,89,[104][105][106][107], a SARS-CoV-2 vaccination program should be implemented in these big cats. There should be more concern about SARS-CoV-2 surveillance in wild animals to minimize the spread of SARS-CoV-2 within the animal population.…”

Evidence of antibodies against SARS-CoV-2 in wild mustelids from Brittany (France)

“…Indeed, they are the most receptive animals to SARS-CoV-2 (Shuai et al, 2020). Like humans, they have the angiotensin-converting enzyme 2 (ACE2) receptor on the cells of the respiratory tract, which facilitates viral penetration (via the spike protein) and infection (Covid-19) (Lean et al, 2021). Infection with SARS-CoV-2 of ferrets ( Mustela putorius furo ), laboratory animals, shows that they remain carriers of the virus for 14 days while the specific antibodies persist for several months (Monchatre-Leroy et al, 2021).…”