ACE2 Expression in the Cat and the Tiger Gastrointestinal Tracts

Abstract

Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). It has been identified in the human gastrointestinal tract (GIT), and SARS-CoV-2 has been isolated in human and animal fecal samples. The aim of the present study was to investigate the expression of ACE2 in the gastrointestinal tract of domestic (cat) and wild (tiger) felines. Samples of the pylorus, duodenum, and distal colon were collected from six cats and one tiger. The tissues were processed for immunofluorescence assay with an anti-human ACE2 antibody. Angiotensin-converting enzyme 2 was widely expressed in the gastrointestinal mucosa of the cats and the tiger. In both the species, ACE2-immunoreactivity (ACE2-IR) was expressed by the mucosal epithelial cells of the GIT and by the enteric neurons. In the cats, ACE2-IR was also expressed by the smooth muscle cells of the blood vessels and the tunica muscularis. The expression of the ACE2 receptor in enteric neurons may support the potential neurotropic properties of SARS-CoV-2. Although the evidence of ACE2-IR in the feline GIT does not necessarily indicate the possibility of viral replication and SARS-CoV-2 spread with stool, the findings in the present study could serve as an anatomical basis for additional studies considering the risk of the SARS-CoV-2 fecal-oral transmission between cats/felids, and between cats/felids and humans.

Keywords: COVID-19; SARS-CoV-2; angiotensin-converting enzyme 2; feline; immunohistochemistry.

Figure 1

Photomicrographs of cryosections of a cat pylorus (a–i) showing angiotensin-converting enzyme 2 immunoreactivity (ACE2-IR) in the gastric mucosa (a–c), myenteric plexus (MP) neurons (d–f) and blood vessels (g–i). (a–c) Moderate ACE2-IR was expressed by the mucosal epithelial cells (open arrow) and secretory cells of the pyloric glands (white arrow). (d–f) White stars indicate two MP neurons expressing bright ACE2-IR which were also immunolabeled for the pan-neuronal marker HuC/HuD. Open stars indicate three MP neurons showing weak ACE2-IR. The smooth muscle cells of the tunica muscularis also showed moderate ACE2-IR as seen in the circular muscle layer (CML). (g–i) The smooth muscle cells (open arrows) of the blood vessels showed moderate ACE2-IR whereas ACE2-IR was undetectable in the endothelial cells (white arrows). Bar: 100 μm.

Figure 2

Photomicrographs of cryosections of a cat duodenum (a–i) and colon (j–l) showing angiotensin-converting enzyme 2 immunoreactivity (ACE2-IR) in the duodenal mucosa (a–f) and submucosal plexus (SMP) neurons (g–i). (a–c) The arrows indicate ACE2-IR expressed by the brush border of enterocytes. (d–f) Open arrows indicate ACE2-IR expressed by the brush border of enterocytes; white arrows indicate the cytoplasmic distribution of the ACE2 immunolabeling. (g–i) Stars indicate the nuclei of SMP neurons showing bright and granular ACE2-IR. Bar: 100 μm.

Figure 3

Photomicrographs of cryosections of the pylorus (a–c), duodenum (d–i), and colon (j–l) of the tiger showing angiotensin-converting enzyme 2 immunoreactivity (ACE2-IR). (a–c) Arrows indicate two pyloric glands in which weak ACE2-IR was expressed by the epithelial cells. (d–f) Arrows indicate two duodenal crypts in which epithelial cells expressed moderate ACE2-IR. (g–i) Stars indicate the submucosal plexus neurons of the duodenum co-expressing ACE2- and HuC/HuD-immunoreactivity. (j–l) Arrows indicate some epithelial cells of the colonic intestinal glands expressing moderate ACE2-IR. Bar: 100 μm.